Methods and kits for diagnosis of multiple sclerosis in probable multiple sclerosis subjects

ABSTRACT

Provided are methods and kits for determining the probability of a subject diagnosed with probable multiple sclerosis to develop definite diagnosis of multiple sclerosis by determining the expression level of polynucleotides which are differentially expressed between subjects diagnosed with probable multiple sclerosis and which further develop definite multiple sclerosis and unaffected subjects. Also provided are methods and kits for selecting a treatment regimen of a subject diagnosed with probable multiple sclerosis.

FIELD AND BACKGROUND OF THE INVENTION

The present invention, in some embodiments thereof, relates to genetic markers which are differentially expressed between subjects diagnosed with probable multiple sclerosis (MS) which further develop the definite diagnosis of MS and control subjects, more particularly, but not exclusively, to methods and kits using same for determining the probability of a subject diagnosed with probable multiple sclerosis to develop a definite diagnosis of multiple sclerosis and for treating subjects diagnosed with probable multiple sclerosis.

Multiple sclerosis (MS) is the most common central nervous system (CNS) disease affecting young adults (disease onset between 20 to 40 years of age), and the third leading cause for disability after trauma and rheumatic diseases. Disease prevalence in USA is 120/100,000, (250,000 to 350,000 cases), and in Israel about 30/100,000. MS is a multifactorial disease that develops in genetically predisposed subjects exposed to yet undefined environmental factors and which results in irreversible neurological disability.

The diagnosis of MS is defined primary by clinical terms and relies on a combination of history, neurological examination and ancillary laboratory and neuro-imaging studies. Typically, at onset of MS, an otherwise healthy person presents with the acute or sub-acute neurological symptomatology (attack). The symptoms usually remain for several days to few weeks, and then partially or completely resolve. The neurological symptoms are accompanied by demyelinating lesions on brain MRI. Thus, the laboratory diagnosis of probable MS is based on: 1) Cerebro-spinal fluid (CSF) evaluation of IgG synthesis, oligoclonal bands; and 2) MRI of the brain and spinal cord. After a period of remission, a second attack will occur. During this period between the first and second attacks, the patient is diagnosed as probable MS. Only when the second attack occurs, the diagnosis of clinically definite MS is established.

In about 85% of the patients with definite diagnosis of MS, the disease course is relapsing-remitting definite MS (RRMS), which is characterized by attacks during which new neurological symptoms and signs appear, or existing neurological symptoms and signs worsen. Usually an attack develops within a period of several days, lasts for 6-8 weeks, and then gradually resolves. During an acute attack, scattered inflammatory and demyelinating CNS lesions produce varying combinations of motor, sensory, coordination, visual, and cognitive impairments, as well as symptoms of fatigue and urinary tract dysfunction. The outcome of an attack is unpredictable in terms of neurological squeal, but it is well established that with each attack, the probability of complete clinical remission decreases, and neurological disability and handicap are liable to develop. In about 15% of patients the disease has a primary progressive course, characterized by gradual onset of neurological symptoms that progress over time. In a subset of patients (about 40%), the disease has a secondary progressive course, i.e., it is first characterized by relapses and remission and then gradually progresses (See FIGS. 4 a-c). The only course of MS in which treatment was effectively established is RRMS. Various immunomodulatory drugs have been shown to reduce the number and severity of acute attacks, and thereby to decrease the accumulation of neurological disability.

The main pathologic findings in MS are the presence of infiltrating mononuclear cells predominantly T lymphocytes and macrophages that surpass the blood brain barrier and induce an active inflammation within the brain and spinal cord, attacking the myelin and resulting in gliotic scars and axonal loss. These inflammatory (acute and chronic) processes can be visualized by brain and spinal cord magnetic resonance imaging (MRI) as hyperintense T2 or hypointense T1 lesions. Thus, MRI examination can serve for the diagnosis of the disease and as a surrogate marker to follow disease activity by measuring lesion load within the brain.

The etiology of MS is still unknown. The pathogenesis of MS involves autoimmune mechanisms associated with autoreactive T cells against myelin antigens. It is well established that not one dominant gene determines genetic susceptibility to develop MS, but rather many genes, each with different influence, are involved. The initial pathogenic process that triggers the disease might be caused by one group of genes, while other groups are probably involved in disease activity and progression (5, 6).

In a previous epidemiological study the present inventors have shown that 57.6% of patients with probable MS experience a second attack within one year from onset, and thus convert to definite MS (7). In other studies, the progression to clinically definite MS in patients with an abnormal brain MRI was 49% and 65% in the first 5 years, 41% and 68% within 2 years, and 24% and 45% within 1 year (8, 9, respectively). Prediction of disease progression rate is especially important during the initial stage, when patients first present with neurological symptomatology and are defined to suffer from probable MS. At this early stage the immunological process of epitope spreading which is associated with exposure of the immune system to myelin antigens is still limited and significant disability has not yet developed.

The potential application of DNA microarray technology for understanding neurological disorders was discussed in a recent review (12). In MS, microarray analysis of brain lesions and brains of mice with experimental allergic encephalomyelitis (EAE)—the experimental animal model of MS —identified genes that contribute to lesion pathology (13). Similarly, different expression of transcribed genes encoding inflammatory cytokines was demonstrated in acute inflammatory brain lesions compared with ‘silent’ lesions without inflammation, using a large-scale gene microarray analysis (14).

In the peripheral blood of MS patients, simultaneous inhibitory and stimulatory effects of inflammatory T cells and macrophages reflect their potential role within the ongoing autoimmune response was reported. Analysis of the expression pattern in peripheral blood mononuclear cells (PBMC) obtained from MS patients during a stable clinical remission revealed 34 genes out of more than 4000 tested that were significantly different from controls (15). In a previous study by the present inventors (16) PBMC gene expression pattern of 26 RRMS patients and 18 healthy subjects demonstrated significantly different pattern of 1109 genes between patients and healthy subjects. This signature contains genes that implicate the underlying processes involved in MS pathogenesis including T-cell activation and expansion, inflammation and apoptosis. To determine disease stage related gene expression signatures MS patients were evaluated during an acute relapse and in remission (16; PCT Pub. No. WO03081201A2, EP1532268A2, AU3214604AH, US20060003327A1, to the present inventors). This analysis demonstrated 721 differentiating genes including genes that play a regulatory role in epitope spreading and in macrophage recruitment to the inflammatory injury. Apoptotic-related genes such as cyclin G1 (CCG1)—the mediator of p53-dependent apoptosis and the caspases 2, 8 and 10 were significantly down-expressed.

SUMMARY OF THE INVENTION

According to an aspect of some embodiments of the present invention there is provided a method of determining a probability of a subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis, comprising determining in a cell of the subject a level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39, wherein an alteration above a predetermined threshold in the level of expression of the at least one polynucleotide sequence in the cell of the subject relative to a level of expression of the at least one polynucleotide sequence in a reference cell is indicative of the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis.

According to an aspect of some embodiments of the present invention there is provided a method of treating a subject diagnosed with probable multiple sclerosis, comprising: (a) determining in a cell of the subject a level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39, wherein an alteration above a predetermined threshold in the level of expression of the at least one polynucleotide sequence in the cell of the subject relative to a level of expression of the at least one polynucleotide sequence in a reference cell is indicative of a probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis, and; (b) selecting a treatment regimen based on the probability; thereby treating the subject diagnosed with probable multiple sclerosis.

According to an aspect of some embodiments of the present invention there is provided a kit for determining a probability of a subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis, comprising no more than 500 isolated nucleic acid sequences, wherein each of the isolated nucleic acid sequences is capable of specifically recognizing at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

According to an aspect of some embodiments of the present invention there is provided a probeset comprising a plurality of oligonucleotides and no more than 500 oligonucleotides wherein each of the plurality of oligonucleotides is capable of specifically recognizing at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

According to some embodiments of the invention, the kit further comprising a reference cell.

According to some embodiments of the invention, each of the isolated nucleic acid sequences or the plurality of oligonucleotides is bound to a solid support.

According to some embodiments of the invention, the plurality of oligonucleotides are bound to the solid support in an addressable location.

According to some embodiments of the invention, the reference cell is of an unaffected subject.

According to some embodiments of the invention, the alteration is upregulation of the expression level of the at least one polynucleotide sequence in the cell of the subject relative to the reference cell, whereas the at least one polynucleotide sequence is selected from the group consisting of SEQ ID NOs:32-58.

According to some embodiments of the invention, the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis is higher than about 75%.

According to some embodiments of the invention, the alteration is downregulation of the expression level of the at least one polynucleotide sequence in the cell of the subject relative to the reference cell, whereas the at least one polynucleotide sequence is selected from the group consisting of SEQ ID NOs:1-31.

According to some embodiments of the invention, the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis is higher than about 75%.

According to some embodiments of the invention, detecting the level of expression is effected using an RNA detection method.

According to some embodiments of the invention, the kit further comprising at least one reagent suitable for detecting hybridization of the isolated nucleic acid sequences and at least one RNA transcript corresponding to the at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

According to some embodiments of the invention, the kit further comprising packaging materials packaging the at least one reagent and instructions for use in determining the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis.

According to some embodiments of the invention, the at least one polynucleotide sequence is as set forth by the polynucleotide sequences of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

According to some embodiments of the invention, the cell of the subject is a blood cell.

According to some embodiments of the invention, wherein said detecting said level of expression is effected using a protein detection method.

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present invention, suitable methods and materials are described below. In case of conflict, the patent specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, with reference to the accompanying drawings. With specific reference now to the drawings in detail, it is stressed that the particulars shown are by way of example and for purposes of illustrative discussion of the preferred embodiments of the present invention only, and are presented in the cause of providing what is believed to be the most useful and readily understood description of the principles and conceptual aspects of the invention. In this regard, no attempt is made to show structural details of the invention in more detail than is necessary for a fundamental understanding of the invention, the description taken with the drawings making apparent to those skilled in the art how the several forms of the invention may be embodied in practice.

In the drawings:

FIGS. 1 a-b depicts the most informative genes differentially expressed between probable MS and healthy subjects. FIG. 1 a—Infogramm of 554 most informative genes (listed in Table 1) discriminated between probable MS patients (N=28) and healthy subjects (N=10); Each row represents a gene and each column represents a patient's sample. FIG. 1 b—PCA analysis demonstrating only two classification errors (marked by circles; 5%) using the 554 most informative genes. Blue dots—healthy subjects, red dots—probable MS patients;

FIGS. 2 a-b depicts the most informative genes differentially expressed between probable MS patients that converted to definite MS during a 2-year follow-up period and healthy subjects. FIG. 2 a—Infogramm of the 1517 most informative genes (listed in Table 2) that discriminated between probable MS patients (N=12) that converted to definite MS during a 2-year follow-up period and healthy subjects (N=11); Each row represents a gene and each column represents a patient's sample. All genes passed FDR criteria at p<0.03 and 8 genes passed Bonfferoni correction at p<3.2×10⁻⁵. FIG. 2 b—PCA applied to the 1517 most informative genes resulted in two clusters, healthy subjects (blue dots) and probable MS patients (red dots) with no classification errors (0 classification errors).

FIG. 3 is a Van-diagram demonstrating intersecting genes between probable which further developed a definite diagnosis of MS (the 1517 genes listed in Table 2 which differentiate between probable patients that developed to definite MS during 2 years follow up and healthy controls) and definite (the 722 genes listed in Table 4 which differentiate between MS patients with a definite diagnosis of MS, i.e., after at least the second neurological attack and healthy controls) PBMC gene expression signatures. Note that the 58 intersecting genes (listed in Table 5) share the same expression pattern, i.e., either upregulation or downregulation relative to control subjects in both subjects diagnosed with probable MS which further developed definite MS within a 2-year period (i.e., probable MS subjects who develop clinical symptoms/MRI pattern which fit the diagnosis of a definite MS) and the subjects diagnosed with definite MS (i.e., an expression pattern determined in subjects with a definite diagnosis of MS);

FIGS. 4 a-c depict the various multiple sclerosis subtypes. FIG. 4 a—a flow chart of the MS clinical subtypes. A subject diagnosed with probable MS can develop a diagnosis of definite MS (in about 85% of the cases) during 5 years follow up period or remain diagnosed as probable MS (in 15% of the cases). Of the subjects diagnosed with definite MS, 85% exhibit a disease course of relapsing-remitting MS (RRMS) and about 15% exhibit a primary progressive course of disease. Of the patients developed RRMS, 40% will develop a secondary progressive MS course. FIG. 4 b schematically illustrates the disease courses of RRMS or secondary progressive MS. FIG. 4 c schematically illustrates the disease course of primary progressive MS with or without attacks/remission periods.

DESCRIPTION OF SPECIFIC EMBODIMENTS OF THE INVENTION

The present invention, in some embodiments thereof, relates to genetic markers which are differentially expressed between probable multiple sclerosis (MS) subjects that further converted to the definite diagnosis of MS and healthy controls. More particularly, but not exclusively, such differentially expressed markers can be used to determine the probability of a subject diagnosed with probable MS to develop a definite diagnosis of MS. In addition, the present invention, in some embodiments thereof, can be used to select a treatment regimen for subjects diagnosed with probable MS based on the expression pattern of such genetic markers.

Before explaining at least one embodiment of the invention in detail, it is to be understood that the invention is not limited in its application to the details set forth in the following description or exemplified by the Examples. The invention is capable of other embodiments or of being practiced or carried out in various ways. Also, it is to be understood that the phraseology and terminology employed herein is for the purpose of description and should not be regarded as limiting.

While reducing the present invention to practice, the present inventors have uncovered genetic markers which are predictive to the definite diagnosis of MS in subjects diagnosed with probable MS, i.e., following the first neurological attack.

As is shown in FIGS. 1 a-b, Table 1 and is described in Example 1 of the Examples section which follows, the present inventors have uncovered 554 genes which are differentially expressed in PBMC between subjects with probable MS and healthy controls. Following a 2-years follow up, the subjects diagnosed with probable MS were divided to those who eventually developed a diagnosis of definite MS (convertors to definite MS) or sustained the diagnosis of probable MS (non-convertors to definite MS). Analysis of the gene expression pattern of probable MS subjects which further converted to definite MS revealed 1517 genes which are differentially expressed as compared to healthy controls (Table 2, FIGS. 2 a-b and Example 2 of the Examples section which follows). In addition, analysis of the gene expression pattern of probable MS subjects which did not convert to definite MS within a period of 2 years revealed 503 genes which are differentially expressed as compared to healthy controls (Table 3, Example 2 of the Examples section which follows). Moreover, comparison of the gene expression pattern of subjects with a definite diagnosis of MS to that of healthy controls revealed 722 genes which are differentially expressed (Table 4, Example 2 of the Examples section which follows). Furthermore, comparison of the differentiating genes between probable MS subjects which further converted to definite MS to that of subjects with the definite diagnosis of MS revealed that the expression pattern of 58 genes is common between the two groups of samples (Table 5, Example 3 of the Examples section which follows). In addition, application of the SVM software based on RBF kernel on a randomly assigned training set of 80% of the 40 probable MS patients revealed optimal sets of genes and their prediction power (average error in test set) of the probability of a subject diagnosed with probable MS to develop the definite diagnosis of MS (Table 6, Example 3 of the Examples section which follows). These results suggest that the expression pattern of each of the 58 genes and/or a combination of several or all of the 58 genes has a predictive value in determining the probability of a subject diagnosed with probable MS to develop the definite diagnosis of MS.

Thus, according to one aspect of the present invention there is provided a method of determining a probability of a subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis. The method is effected by determining in a cell of the subject a level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39, wherein an alteration above a predetermined threshold in the level of expression of the at least one polynucleotide sequence in the cell of the subject relative to a level of expression of the at least one polynucleotide sequence in a reference cell is indicative of the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis.

As used herein, the phrase “a subject diagnosed with probable multiple sclerosis” refers to a mammal, preferably a human being, who is diagnosed with probable multiple sclerosis, e.g., a subject who experienced one neurological attack affecting the CNS and accompanied by demyelinating lesions on brain magnetic resonance imaging (MRI). The neurological attack can involve acute or sub-acute neurological symptomatology (attack) manifested by various clinical presentations like unilateral loss of vision, vertigo, ataxia, incoordination, gait difficulties, sensory impairment characterized by paresthesia, dysesthesia, sensory loss, urinary disturbances until incontinence, diplopia, dysarthria, various degrees of motor weakness until paralysis, cognitive decline either as a monosymptomatic or in combination. The symptoms usually remain for several days to few weeks, and then partially or completely resolve.

The diagnosis of probable MS can also include laboratory tests involving evaluation of IgG synthesis and oligoclonal bands (immunoglobulins found in 85-95% of subjects diagnosed with definite MS) in the cerebrospinal fluid (CSF, obtained by e.g., lumbar puncture) which provide evidence of chronic inflammation of the central nervous system. Combined with MRI of the brain and spinal cord and clinical data, the presence of oligoclonal bands can help make a definite diagnosis of MS.

As used herein, the phrase “determining a probability” refers to the likelihood of a subject diagnosed with probable MS to develop the definite diagnosis of MS within a certain time period. According to an embodiment of the invention, such probability can be high, e.g., more than 51%, at least 60%, at least 70%, at least 80%, at least 85%, at least 87%, at least 90%, at least 95%, at least 99%, e.g., 100%, that a subject diagnosed with probable MS will develop the definite diagnosis of MS. It will be appreciated that the time period during which the subject diagnosed with probable MS will convert to the definite diagnosis of MS can be within 1 year since onset of probable MS, within 2-3 years, within 3-5 years, or more.

As used herein the phrase “develop definite multiple sclerosis” refers to a subject who is diagnosed with probable MS and which experiences at least a second neurological attack affecting the CNS and accompanied by demyelinating lesions on brain magnetic resonance imaging (MRI), wherein the neurological attacks are associated with the appearance of new neurological symptoms and signs or the worsening of existing neurological symptoms and signs. It will be appreciated that the disease course of patients diagnosed with definite MS can be a relapsing-remitting multiple sclerosis (RRMS) (occurring in 85% of the patients), a primary progressive multiple sclerosis (occurring in 15% of the patients) or a secondary progressive multiple sclerosis (occurring in 40% of the RRMS patients; see FIG. 4).

As mentioned, the method according to this aspect of the present invention is effected by determining in a cell of the subject a level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

According to an embodiment of the invention, the method is effected by determining in a cell of the subject a level of expression of at least two, at least three, at least four, at least five, at least six, at least seven, at least eight, at least nine, at least 10 polynucleotide sequences, at least 20, at least 30, at least 40, at least 50 polynucleotide sequences, e.g., 58 polynucleotide sequences selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39, wherein an alteration above a predetermined threshold in the level of expression of each of the polynucleotide sequences in the cell of the subject relative to a level of expression of the same polynucleotide sequences in a reference cell is indicative of the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis.

As mentioned above, shown in Table 6 and described in Example 3 of the Examples section which follows, the prediction power of the selected polynucleotides set forth by SEQ ID NOs:1-58 in determining the probability of a subject diagnosed with probable MS to develop definite MS within 2 years was computed using the SVM based on RBF kernel when applied on a set of 40 probable MS subjects, randomly divided to 80% as training set and 20% as test set. The polynucleotide sequence exhibiting the best prediction power as a single gene, which can be used to determine the probability of a subject diagnosed with probable MS to develop definite multiple sclerosis is set forth in SEQ ID NO:4 (average error: 0.216; prediction accuracy of 78.4%).

As is further shown in Table 6 (Example 3) several groups of genes can predict the probability of a subject diagnosed with probable MS to develop a definite multiple sclerosis within 2 years with about 87% accuracy (average error of about 0.13).

According to an embodiment of the invention, the polynucleotide sequences which expression level are determined in the cell of the subject diagnosed with probable MS are those depicted in any of the following groups of row numbers of Table 6 in Example 3 of the Examples section which follows: rows 1-33; rows 1-34; rows 1-35; rows 1-40; rows 1-44; and rows 1-45.

As is further shown in Table 6 (Example 3) several groups of genes can predict the probability of a subject diagnosed with probable MS to develop a definite multiple sclerosis within 2 years with about 84-86% accuracy (average error of about 0.14-0.16).

According to an embodiment of the invention, the polynucleotide sequences which expression level are determined in the cell of the subject diagnosed with probable MS are those depicted in any of the following groups of row numbers of Table 6 in Example 3 of the Examples section which follows: rows 1-6; rows 1-14; rows 1-15; rows 1-16; rows 1-17; rows 1-18; rows 1-19; rows 1-29; rows 1-31; rows 1-32; rows 1-36; rows 1-37; rows 1-38; rows 1-39; rows 1-40; rows 1-41; rows 1-42; rows 1-43; rows 1-46; rows 1-47; rows 1-48; rows 1-49; rows 1-50; and rows 1-52.

As is further shown in Table 6 (Example 3) several groups of genes can predict the probability of a subject diagnosed with probable MS to develop a definite multiple sclerosis diagnosis with about 80-83% accuracy (average error of about 0.17-0.20).

According to an embodiment of the invention, the polynucleotide sequences which expression level are determined in the cell of the subject diagnosed with probable MS are those depicted in any of the following groups of row numbers of Table 6 in Example 3 of the Examples section which follows: rows 1-7; rows 1-8; rows 1-9; rows 1-10; rows 1-12; rows 1-13; rows 1-20; rows 1-21; rows 1-22; rows 1-23; rows 1-24; rows 1-25; rows 1-26; rows 1-27; rows 1-28; rows 1-30; rows 1-51; rows 1-53; rows 1-54; rows 1-55; rows 1-56; rows 1-57; and rows 1-58.

As is further shown in Table 6 (Example 3) several groups of genes can predict the probability of a subject diagnosed with probable MS to develop a definite multiple sclerosis diagnosis with about 75-79% accuracy (average error of about 0.21-0.25).

According to an embodiment of the invention, the polynucleotide sequences which expression level are determined in the cell of the subject diagnosed with probable MS are those depicted in any of the following groups of row numbers of Table 6 in Example 3 of the Examples section which follows: rows 1-2; rows 1-3; rows 1-4; rows 1-5; and rows 1-11.

As used herein, the phrase “level of expression” refers to the degree of gene expression and/or gene product activity in a specific cell. For example, up-regulation or down-regulation of various genes can affect the level of the gene product (i.e., RNA and/or protein) in a specific cell.

As used herein the phrase “a cell of the subject” refers to any cell content and/or cell secreted content which contains RNA and/or proteins of the subject.

Examples include a blood cell, a bone marrow cell, a cell obtained from any tissue biopsy (e.g., CSF, brain biopsy), body fluids such as plasma, serum, saliva, spinal fluid, lymph fluid, the external sections of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, sputum and milk. According to an embodiment of the invention, the cell is a blood cell (e.g., white blood cells, macrophages, B- and T-lymphocytes, monocytes, neutrophiles, eosinophiles, and basophiles) which can be obtained using a syringe needle from a vein of the subject. It will be appreciated that PBMC is the most accessible tissue and could be useful as a minimally invasive approach for gene expression differential diagnosis. It should be noted that a “cell of the subject” may also optionally comprise a cell that has not been physically removed from the subject (e.g., in vivo detection).

According to an embodiment of the invention, the white blood cell comprises peripheral blood mononuclear cells (PBMC). The phrase, “peripheral blood mononuclear cells (PBMCs)” as used herein, refers to a mixture of monocytes and lymphocytes. Several methods for isolating white blood cells are known in the art. For example, PBMCs can be isolated from whole blood samples using density gradient centrifugation procedures. Typically, anticoagulated whole blood is layered over the separating medium. At the end of the centrifugation step, the following layers are visually observed from top to bottom: plasma/platelets, PBMCs, separating medium and erythrocytes/granulocytes. The PBMC layer is then removed and washed to remove contaminants (e.g., red blood cells) prior to determining the expression level of the polynucleotide(s) therein.

It will be appreciated that the cell of the subject can be obtained at any time, e.g., immediately after an attack or at any time during remission.

According to preferred embodiments of the present invention, detecting the level of expression of the polynucleotide sequences of the present invention is effected using RNA or protein molecules which are extracted from the cell of the subject.

Methods of extracting RNA or protein molecules from cells of a subject are well known in the art.

Once obtained, the RNA or protein molecules can be characterized for the expression and/or activity level of various RNA and/or protein molecules using methods known in the arts.

Non-limiting examples of methods of detecting RNA molecules in a cell sample include Northern blot analysis, RT-PCR, RNA in situ hybridization (using e.g., DNA or RNA probes to hybridize RNA molecules present in the cells or tissue sections), in situ RT-PCR (e.g., as described in Nuovo G J, et al. Am J Surg Pathol. 1993, 17: 683-90; Komminoth P, et al. Pathol Res Pract. 1994, 190: 1017-25), and oligonucleotide microarray (e.g., by hybridization of polynucleotide sequences derived from a sample to oligonucleotides attached to a solid surface [e.g., a glass wafer) with addressable location, such as Affymetrix microarray (Affymetrix®, Santa Clara, Calif.)].

Non-limiting examples of methods of detecting the level and/or activity of specific protein molecules in a cell sample include Enzyme linked immunosorbent assay (ELISA), Western blot analysis, radio-immunoassay (RIA), Fluorescence activated cell sorting (FACS), immunohistochemical analysis, in situ activity assay (using e.g., a chromogenic substrate applied on the cells containing an active enzyme), in vitro activity assays (in which the activity of a particular enzyme is measured in a protein mixture extracted from the cells).

For example, in case the detection of the expression level of a secreted protein is desired, ELISA assay may be performed on a sample of fluid obtained from the subject (e.g., serum), which contains cell-secreted content.

As used herein the phrase “reference cell” refers to any cell as described hereinabove of an unaffected subject (i.e., a subject devoid of any neurological attack resembling MS or probable MS) such as a healthy subject, which can be an age and/or gender-matched unaffected subject (e.g., a healthy subject from the same age and/or gender as of the subject diagnosed with probable MS). Such a reference cell can be a blood cell, a bone marrow cell, a cell obtained from any tissue biopsy (e.g., CSF), body fluids such as plasma, serum, saliva, spinal fluid, lymph fluid, the external sections of the skin, respiratory, intestinal, and genitourinary tracts, tears, saliva, sputum and milk. It will be appreciated that the level of expression of the above referenced polynucleotides/polypeptides may be obtained from scientific literature.

Since as is shown in Table 5 and is described in Example 2 of the Examples section which follows, 27 polynucleotide sequences displayed elevated expression in the subjects diagnosed with probable MS which further developed the definite diagnosis of MS relative to healthy subjects, in order to determine the probability of a subject diagnosed with probable MS to develop definite MS, the level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:32-58 is determined and compared to the level of expression of the same polynucleotide sequences in a reference cell derived from an unaffected subject, wherein an upregulation (increase) in the expression level of the at least one polynucleotide sequence above a predetermined threshold relative to the reference cell is indicative of a high probability (e.g., higher than about 75%, about 80%, about 85%, about 87%) of the subject diagnosed with probable MS to develop definite MS (e.g., to convert to definite MS within a period of about 2 years). On the other hand, downregulation or no significant change in the level of expression, of the same at least one polynucleotide sequence relative to the reference cell is indicative of low probability (e.g., less than about 75%, e.g., less than 50%, e.g., less than 30%) of the subject diagnosed with probable MS to develop definite MS (e.g., to convert to definite MS within a period of about 2 years). It will be appreciated that such a subject can eventually develop definite MS following a longer period of time, e.g. more than 2 years, e.g., 10-20 years.

Additionally or alternatively, since as is further shown in Table 2 and is described in Example 2 of the Examples section which follows, the level of expression of 31 polynucleotide sequences was downregulated in subjects diagnosed with probable MS relative to the healthy control subjects, in order to determine the probability of a subject diagnosed with probable MS to develop definite MS, the level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:1-31 is determined and compared to the level of expression of the same polynucleotide sequences in a reference cell derived from an unaffected subject, wherein downregulation (decrease) in the expression level of the at least one polynucleotide sequence above a predetermined threshold relative to the reference cell is indicative of high probability (e.g., higher than about 75%, about 80%, about 85%, about 87%) of the subject diagnosed with probable MS to develop definite MS (e.g., to convert to definite MS within a period of about 2 years). On the other hand, upregulation or no significant change in the level of expression of the same at least one polynucleotide sequence relative to the reference cell is indicative of low probability (e.g., lower than 75%, e.g., less than 50%, e.g., less than 30%) of the subject diagnosed with probable MS to develop definite MS (e.g., to convert to definite MS within a period of about 2 years). It will be appreciated that such a subject can eventually develop definite MS following a longer period of time, e.g., more than 2 years.

As used herein the phrase “an alteration above a predetermined threshold” refers to the increase or decrease (i.e., degree of upregulation or downregulation, respectively) which is higher than a predetermined threshold such as at least twice, at least three times, at least four times, at least five times, at least six times, at least seven times, at least eight times, at least nine times, at least 10 times, at least 20 times, at least 50 times, at least 100 times, at least 500 times relative to the reference cell.

For example, as is shown in Table 5, while the level of expression of the polynucleotide sequences set forth by SEQ ID NOs:1-16, is at least twice lower in subjects diagnosed with probable MS which further developed definite MS as compared to unaffected subjects, the level of expression of the polynucleotide sequences set forth by SEQ ID NOs:17-26, the polynucleotide sequences set forth by SEQ ID NOs:27-29, or the polynucleotides set forth by SEQ ID NOs:30-31 is at least 5, 10, or 50 times, respectively, lower in cells of subjects diagnosed with probable MS which further developed definite MS as compared to unaffected, healthy subjects.

In addition, as is further shown in Table 2, while the level of expression of the polynucleotide sequences set forth by SEQ ID NOs:32-46, is at least twice higher in subjects diagnosed with probable MS which further developed definite MS as compared to unaffected, healthy subjects, the level of expression of the polynucleotide sequences set forth by SEQ ID NOs:47-52, the polynucleotides set forth by SEQ ID NOs:53-56, or the polynucleotide set forth by SEQ ID NOs:57-58 is at least 5, 10, or 50 times, respectively, higher in cells of subjects diagnosed with probable MS which further developed definite MS as compared to unaffected, healthy subjects.

It will be appreciated that higher fold change in the expression level of the at least one polynucleotide in the cell of the subject relative the reference cell, and/or alteration in the level of expression of the polynucleotides which exhibit high fold change in Table 5 of Example 2 (e.g., SEQ ID NOs:17-26 and/or 47-52, SEQ ID NOs:27-29 and/or 53-56, 30-31 and/or 57-58), and/or alteration above the predetermined threshold in a significant number of polynucleotides from the polynucleotides set forth by SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39 (e.g., at least 30, at least 40, at least 45, at least 50, or 58) will indicate high probability that the subject diagnosed with probable MS will develop definite MS within a short period of time (during 2 years).

Thus, the method of determining the probability of a subject diagnosed with probable MS to develop definite MS according to the invention enables the classification of probable MS patients to those that will develop definite MS within a predetermined time (e.g., about 2 years, fast convertors) and to those who will sustain the diagnosis of probable MS and will either not convert to definite MS or will convert to definite MS following an extended period of time (e.g., more than 2 years, e.g., at least 10 years).

Thus, the teachings of the present invention can be used to improve the diagnosis of definite MS following the first neurological attack, without needing to rely on the appearance of the second neurological attack.

It will be appreciated that determining the probability of a subject diagnosed with probable MS to develop definite MS can be used to select the treatment regimen of the subject and thereby to treat the subject diagnosed with probable MS.

Thus, according to an aspect of some embodiments of the present invention there is provided a method of treating a subject diagnosed with probable multiple sclerosis. The method is effected by: (a) determining in a cell of the subject a level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 11, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39, wherein an alteration above a predetermined threshold in the level of expression of the at least one polynucleotide sequence in the cell of the subject relative to a level of expression of the at least one polynucleotide sequence in a reference cell is indicative of a probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis, and (b) selecting a treatment regimen based on the probability, thereby treating the subject diagnosed with probable multiple sclerosis.

As used herein the phrase “treating” refers to inhibiting or arresting the development of a pathology [multiple sclerosis, e.g., RRMS or progressive (e.g., primary or secondary) MS] and/or causing the reduction, remission, or regression of a pathology and/or optimally curing the pathology. Those of skill in the art will understand that various methodologies and assays can be used to assess the development of a pathology, and similarly, various methodologies and assays may be used to assess the reduction, remission or regression of the pathology.

According to an embodiment of the invention, when the probability as determined according to the method of the invention of the subject diagnosed with probable MS to develop definite MS is high [e.g., at least 89.9% that the subject will develop definite MS within 2 years], the treatment regimen selected for treating such a subject comprises preventive medications which will prevent the reaction leading to neurological disability. It will be appreciated that the currently available medications for treating definite MS are not allowed for treating subjects diagnosed with probable MS. Thus, teachings of the invention can be used to prevent the neurological deterioration of subjects diagnosed with probable MS.

Thus, by determining the probability of the subject diagnosed with probable MS to develop definite MS, the subject can be treated early, prior to experiencing the second neurological attack, with suitable therapeutics that can prevent deterioration of clinical symptoms and can increase the chances of achieving cure and remission of symptoms in the affected subjects.

It will be appreciated that classification of subjects diagnosed with probable MS to those that will convert fast to definite MS and to those that will sustain the diagnosis of probable MS can be also used in order to assess the efficacy of a treatment regimen on probable MS patients which are likely to develop definite MS. Thus, by treating subjects with probable MS and high probability to develop definite MS (as determined by the method of the invention) with candidate preventive and/or therapeutic drugs and monitoring the subjects' health in terms of MS progression (e.g., EDSS evaluation and number of relapses), the efficacy of the drugs can be assessed.

The teachings of the invention are of utmost importance and have relevant medical, economical and social aspects. While the MS disease prevalence in USA is at the range of 250.000 to 350.000 cases, the annual cost of MS in USA is anticipated to be 34,000 $ per patient, leading to 2.2 million $ total lifetime cost per patient or 6.8 billion $ yearly, in a conservative estimate of the national annual cost. The possibility to early identify the patients which will develop definite MS among the patients with the diagnosis of probable MS is of utmost importance, as it would be possible to start preventive treatment early and delay accumulation of irreversible neurological disability, inhibition/suppression of disease progression as well as reduce annual cost of disease.

It will be appreciated that the reagents utilized by any of the methods of the present invention which are described hereinabove can form a part of a diagnostic kit/article of manufacture.

The kit of the invention comprises at least one and no more than 500 isolated nucleic acid sequences, e.g., at least 2 and no more than 500 isolated nucleic acid sequences, e.g., at least 4 and no more than 400 isolated nucleic acid sequences, e.g., at least 6 and no more than 300 isolated nucleic acid sequences, e.g., at least 8 and no more than 200 isolated nucleic acid sequences, e.g., at least 2 and no more than 100 isolated nucleic acid sequences, e.g., at least 2 and no more than 58 isolated nucleic acid sequences, wherein each of the at least one and no more than 500 isolated nucleic acid sequences is capable of specifically recognizing at least one specific polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

The isolated nucleic acid sequences included in the kit of the present invention can be single-stranded or double-stranded, naturally occurring or synthetic nucleic acid sequences such as oligonucleotides, RNA molecules, genomic DNA molecules, cDNA molecules and/or cRNA molecules. The isolated nucleic acid sequences of the kit can be composed of naturally occurring bases, sugars, and covalent internucleoside linkages (e.g., backbone), as well as non-naturally occurring portions, which function similarly to respective naturally occurring portions.

Synthesis of the isolated nucleic acid sequences of the kit can be performed using enzymatic synthesis or solid-phase synthesis. Equipment and reagents for executing solid-phase synthesis are commercially available from, for example, Applied Biosystems. Any other means for such synthesis may also be employed; the actual synthesis of the oligonucleotides is well within the capabilities of one skilled in the art and can be accomplished via established methodologies as detailed in, for example: Sambrook, J. and Russell, D. W. (2001), “Molecular Cloning: A Laboratory Manual”; Ausubel, R. M. et al., eds. (1994, 1989), “Current Protocols in Molecular Biology,” Volumes I-III, John Wiley & Sons, Baltimore, Md.; Perbal, B. (1988), “A Practical Guide to Molecular Cloning,” John Wiley & Sons, New York; and Gait, M. J., ed. (1984), “Oligonucleotide Synthesis”; utilizing solid-phase chemistry, e.g. cyanoethyl phosphoramidite followed by deprotection, desalting, and purification by, for example, an automated trityl-on method or HPLC.

According to an embodiment of the invention, each of the isolated nucleic acid sequences included in the kit of present invention comprises at least 10 and no more than 50 nucleic acids, e.g., at least 15 and no more than 45, e.g., between 15-40, e.g., between 20-35, e.g., between 20-30, e.g., between 20-25 nucleic acids.

According to an embodiment of the invention the kit includes at least one reagent as described hereinabove which is suitable for recognizing the at least one specific polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39. Examples include reagents suitable for hybridization or annealing of a specific polynucleotide of the kit to a specific target polynucleotide sequence (e.g., RNA transcript derived from the cell of the subject or a cDNA derived therefrom) such as formamide, sodium chloride, and sodium citrate), reagents which can be used to labeled polynucleotides (e.g., radiolabeled nucleotides, biotinylated nucleotides, digoxigenin-conjugated nucleotides, fluorescent-conjugated nucleotides) as well as reagents suitable for detecting the labeled polynucleotides (e.g., antibodies conjugated to fluorescent dyes, antibodies conjugated to enzymes, radiolabeled antibodies and the like).

Additionally or alternatively, the kit of the present invention comprises at least one reagent suitable for detecting the expression level and/or activity of at least one polypeptide encoded by at least one polynucleotides selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39. Such a reagent can be, for example, an antibody capable of specifically binding to at least one epitope of the polypeptide. Additionally or alternatively, the reagent included in the kit can be a specific substrate capable of binding to an active site of the polypeptide. In addition, the kit may also include reagents such as fluorescent conjugates, secondary antibodies and the like which are suitable for detecting the binding of a specific antibody and/or a specific substrate to the polypeptide.

According to an embodiment of the invention the kit includes a reference cell which comprises a cell of an unaffected subject as described hereinabove.

According to an embodiment of the invention, the kit of the invention includes packaging material packaging the at least one reagent and a notification in or on the packaging material. Such a notification identifies the kit for use in determining the probability of a subject diagnosed with probable MS to develop definite MS and selecting a treatment regimen of a subject and thereby treating the subject diagnosed with probable MS. The kit may also include instructions for use in determining the probability of a subject diagnosed with probable MS to develop definite MS and selecting a treatment regimen of a subject and thereby treating the subject diagnosed with probable MS. The kit may also include appropriate buffers and preservatives for improving the shelf-life of the kit.

It will be appreciated that the isolated nucleic acid sequences described hereinabove (e.g., oligonucleotides) can form a part of a probeset. The probeset comprises a plurality of oligonucleotides and no more than 500 oligonucleotides wherein each of the plurality of oligonucleotides is capable of specifically recognizing at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

It will be appreciated that the isolated nucleic acid sequences included in the kit or the probeset of the present invention can be bound to a solid support e.g., a glass wafer in a specific order, i.e., in the form of a microarray. Alternatively, isolated nucleic acid sequences can be synthesized directly on the solid support using well known prior art approaches (Seo T S, et al., 2004, Proc. Natl. Acad. Sci. USA, 101: 5488-93.). In any case, the isolated nucleic acid sequences are attached to the support in a location specific manner such that each specific isolated nucleic acid sequence has a specific address on the support (i.e., an addressable location) which denotes the identity (i.e., the sequence) of that specific isolated nucleic acid sequence.

According to preferred embodiments of the present invention the microarray comprises no more than 500 isolated nucleic acid sequences, wherein each of the isolated nucleic acid sequences is capable of specifically recognizing at least one specific polynucleotide sequence selected from the group consisting of SEQ ID NOs: 4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39.

As used herein the term “about” refers to ±10%.

Additional objects, advantages, and novel features of the present invention will become apparent to one ordinarily skilled in the art upon examination of the following examples, which are not intended to be limiting. Additionally, each of the various embodiments and aspects of the present invention as delineated hereinabove and as claimed in the claims section below finds experimental support in the following examples.

EXAMPLES

Reference is now made to the following examples, which together with the above descriptions; illustrate the invention in a non-limiting fashion.

Generally, the nomenclature used herein and the laboratory procedures utilized in the present invention include molecular, biochemical, microbiological and recombinant DNA techniques. Such techniques are thoroughly explained in the literature. See, for example, “Molecular Cloning: A laboratory Manual” Sambrook et al., (1989); “Current Protocols in Molecular Biology” Volumes I-III Ausubel, R. M., ed. (1994); Ausubel et al., “Current Protocols in Molecular Biology”, John Wiley and Sons, Baltimore, Md. (1989); Perbal, “A Practical Guide to Molecular Cloning”, John Wiley & Sons, New York (1988); Watson et al., “Recombinant DNA”, Scientific American Books, New York; Birren et al. (eds) “Genome Analysis: A Laboratory Manual Series”, Vols. 1-4, Cold Spring Harbor Laboratory Press, New York (1998); methodologies as set forth in U.S. Pat. Nos. 4,666,828; 4,683,202; 4,801,531; 5,192,659 and 5,272,057; “Cell Biology: A Laboratory Handbook”, Volumes I-III Cellis, J. E., ed. (1994); “Current Protocols in Immunology” Volumes I-III Coligan J. E., ed. (1994); Stites et al. (eds), “Basic and Clinical Immunology” (8th Edition), Appleton & Lange, Norwalk, Conn. (1994); Mishell and Shiigi (eds), “Selected Methods in Cellular Immunology”, W. H. Freeman and Co., New York (1980); available immunoassays are extensively described in the patent and scientific literature, see, for example, U.S. Pat. Nos. 3,791,932; 3,839,153; 3,850,752; 3,850,578; 3,853,987; 3,867,517; 3,879,262; 3,901,654; 3,935,074; 3,984,533; 3,996,345; 4,034,074; 4,098,876; 4,879,219; 5,011,771 and 5,281,521; “Oligonucleotide Synthesis” Gait, M. J., ed. (1984); “Nucleic Acid Hybridization” Hames, B. D., and Higgins S. J., eds. (1985); “Transcription and Translation” Hames, B. D., and Higgins S. J., Eds. (1984); “Animal Cell Culture” Freshney, R. I., ed. (1986); “Immobilized Cells and Enzymes” IRL Press, (1986); “A Practical Guide to Molecular Cloning” Perbal, B., (1984) and “Methods in Enzymology” Vol. 1-317, Academic Press; “PCR Protocols: A Guide To Methods And Applications”, Academic Press, San Diego, Calif. (1990); Marshak et al., “Strategies for Protein Purification and Characterization—A Laboratory Course Manual” CSHL Press (1996); all of which are incorporated by reference as if fully set forth herein. Other general references are provided throughout this document. The procedures therein are believed to be well known in the art and are provided for the convenience of the reader. All the information contained therein is incorporated herein by reference.

General Materials and Experimental Methods

Study design and study subjects—40 patients with probable MS of up to 3 months duration according to Poser's criteria (1983, CPMS C3: 1 attack, at least 1 clinical manifestation in addition to positive brain MRI signifying paraclinical evidence) were included in the study. Positive brain MM was defined according to Fazekas's criteria (1999) by at least 4 focal lesions involving the white matter or 3 lesions if one is periventricular; ≧3 mm in diameter, each. For the evaluation of probable MS related transcription fingerprints the large-scale gene expression profile of patients was compared with the data of 10 sex- and age-matched healthy subjects. Verification of probable PBMC gene expression signature was performed on Signed written informed consent was obtained from all participants.

Clinical neurological assessment—Neurological examination and assessment of disability was performed by the Expanded Disability Status Scale (EDSS) score (17) performed at screening, baseline visit, and at 24, 36 and 48 weeks of follow-up visits. The occurrence of a second acute attack, the time to second attack (progression to definite MS) and the change in neurological disability assessed by the EDSS were recorded in each patient. Second attack was defined as the onset of new neurological symptoms or worsening of previous ones occurring at least 30 days after the first attack, lasting for at least 48 hours and involving an objective increase by at least 0.5 point in the EDSS.

MRI examination—Brain MRI was performed using a 3.0 Tesla Imager (GE): Axial dual spin-echo (PD and T2 sequences) and T1-weighted images before and after intravenous administration of Gd-DTPA. Brain lesion load was quantified using the MSAnalyze software (18). This automated technique is based on several mathematical algorithms (e.g., Bayesian classification, near-neighborhood) leading to brain tissue segmentation enabling precise 3-dimensional lesions' identification and volumetric quantification.

PBMC preparation—Blood sample (20 ml) was drawn from all study subjects. No corticosteroid treatment was given for at least 4 weeks prior to blood drawing. PBMC were separated on Ficoll hypaque, washed with PBS and the pellet frozen in liquid nitrogen.

RNA extraction—Frozen PBMC were homogenized in ice cold trizol and total RNA extracted and used as a template for double stranded cDNA synthesis (Affymetrix, Santa Clara, Calif.). RNA quantity was determined by optical density measurements at 260 nm and its quality by running the RNA on a formamide-formaldehyde denaturing gel.

Preparation of labeled cRNA—Double stranded cDNA was performed using a cDNA synthesis kit (Life Technologies Superscript cDNA Synthesis System) with an oligo (dT) primer containing a T7 RNA polymerase promoter site added to the 3′. The cDNA was used as a template for in vitro transcription with biotin labeled nucleotides (Enzo Diagnostics). Labeled cRNA was used for hybridization.

Hybridization of microarrays—Each Genechip array (U133A) was hybridized with 10 μg/200 μl hybridization mix, stained with streptavidin phycoerythrin (Molecular Probes), hybridized with biotin labeled anti-streptavidin phycoerythrin antibody, re-stained with streptavidin phycoerythrin and scanned (Hewlett Packard, GeneArray-™ scanner G2500A).

Data analysis—Data were analyzed using ScoreGene software. To correct for multiple testing the False Discovery Rate (FDR) method and the stringent Bonferroni correction were applied. Overabundance analysis was performed to examine the observed results in comparison to expected results. To assess and validate the predictive power of the gene expression signature, the following methods were applied: Leave-One-Out-Cross-Validation (LOOCV) (21; Ben-Dor A et al., 2000) Principal Component Analysis (PCA), and Support vector machine (SVM) [(http://ro.utia.cz/fs/fs_algorithms.html), (19, 20). The study involves various comparisons between subjects of the data set. Due to the reasons of controls compatibility, the number of controls changes from one comparison to another.

Computation of the average error in determining which probable multiple sclerosis (MS) subjects exhibit high probability (predisposition) to develop the definite diagnosis of MS—For each of the 58 differentiating genes (SEQ ID NOs:1-58) the sample of 40 probable MS patients was randomly divided into 80% as a “training set” and 20% as a “test set”. The SVM used RBF (radial basic function) kernel to build a model based on the “training set”, which was further tested on the “test set” while saving the error rate. This procedure was repeated 25 times for each gene and the average error for each gene was calculated. Genes with the lowest average error were selected. Then, for each selected gene, the remaining genes were added one after the other, by selecting the next gene such that the average error after 25 repeats of the group of genes including the new gene has the lowest average error as compared to the addition of another gene. This process was repeated 57 times for each additional genes added to the previous group of genes. The results are shown in Table 6 and described in Example 3 hereinbelow.

Example 1 Identification of Transcripts Differentiating Between Probable MS and Healthy Subjects

Experimental and Statistical Results

Analysis of large scale gene expression pattern—Analysis of large-scale gene expression patterns of PBMC samples obtained from 28 patients with probable MS (mean±SE, age 36.0±1.9 years, EDSS 1.5±0.2) and 10 healthy matched controls was performed. Gene expression patterns of PBMC in probable MS patients were significantly different from healthy subject. Table 1, hereinbelow, depicts 554 genes that passed the 95% confidence level in all 3 statistical scores (TNoM, Info, T-test); 352 genes were over-expressed and 202 under-expressed. These genes were defined as the most informative (FIG. 1 a). PCA performed on the 554 most informative genes divided all samples into two separated clusters that represented probable MS patients and healthy subjects with only 2 (5%) classification errors (FIG. 1 b).

TABLE 1 Differentially expressed markers between probable multiple sclerosis subjects and healthy controls GenBank Probeset Acc. No. Dir Gene Symbol 1494_f_at M33318 −1 CYP2A6 200797_s_at AI275690 −1 MCL1 200798_x_at NM_021960 −1 MCL1 201041_s_at NM_004417 −1 DUSP1 201044_x_at AA530892 −1 DUSP1 201109_s_at AV726673 −1 THBS1 201110_s_at NM_003246 −1 THBS1 201235_s_at BG339064 −1 BTG2 201236_s_at BG339064 −1 BTG2 201464_x_at BC002646 −1 JUN 201473_at NM_002229 −1 JUNB 201489_at BC005020 −1 PPIF 201490_s_at NM_005729 −1 PPIF 201502_s_at NM_020529 −1 NFKBIA 201531_at NM_003407 −1 ZFP36 201631_s_at NM_003897 −1 IER3 201647_s_at NM_005506 −1 SCARB2 201668_x_at AW163148 −1 MARCKS 201669_s_at NM_002356 −1 MARCKS 201670_s_at M68956 −1 MARCKS 201693_s_at NM_001964 −1 EGR1 201694_s_at NM_001964 −1 EGR1 202672_s_at NM_001674 −1 ATF3 204224_s_at NM_000161 −1 GCH1 201884_at NM_004363 −1 CEACAM5 202014_at NM_014330 −1 PPP1R15A 202068_s_at NM_000527 −1 LDLR 202081_at NM_004907 −1 IER2 202286_s_at J04152 −1 TACSTD2 202340_x_at NM_002135 −1 NR4A1 202570_s_at NM_014902 −1 DLGAP4 202637_s_at AI608725 −1 ICAM1 202638_s_at NM_000201 −1 ICAM1 202643_s_at AI738896 −1 TNFAIP3 202644_s_at NM_006290 −1 TNFAIP3 202859_x_at NM_000584 −1 IL8 202895_s_at D86043 −1 PTPNS1 202924_s_at AF006005 −1 PLAGL2 202925_s_at NM_002657 −1 PLAGL2 203317_at NM_012455 −1 PSD4 203394_s_at BE973687 −1 HES1 203470_s_at AI433595 −1 PLEK 203471_s_at NM_002664 −1 PLEK 203672_x_at U12387 −1 TPMT 203927_at NM_004556 −1 NFKBIE 204103_at NM_002984 −1 CCL4 204393_s_at NM_001099 −1 ACPP 204440_at NM_004233 −1 CD83 204469_at NM_002851 −1 PTPRZ1 204470_at NM_001511 −1 CXCL1 204533_at NM_001565 −1 CXCL10 204748_at NM_000963 −1 PTGS2 204794_at NM_004418 −1 DUSP2 204897_at AA897516 −1 PTGER4 204907_s_at AI829875 −1 BCL3 204970_s_at NM_002359 −1 MAFG 205045_at NM_007202 −1 AKAP10 205067_at NM_000576 −1 IL1B 205114_s_at NM_002983 −1 CCL3, CCL3L1 205115_s_at NM_016196 −1 RBM19 205207_at NM_000600 −1 IL6 205220_at NM_006018 −1 GPR109B 205318_at NM_004984 −1 KIF5A 205558_at NM_004620 −1 TRAF6 205643_s_at NM_004576 −1 PPP2R2B 205681_at NM_004049 −1 BCL2A1 205767_at NM_001432 −1 EREG 206025_s_at AW188198 −1 TNFAIP6 206087_x_at NM_000410 −1 HFE 206157_at NM_002852 −1 PTX3 206207_at NM_001828 −1 CLC 206256_at NM_001308 −1 CPN1 206295_at NM_001562 −1 IL18 206704_at NM_000084 −1 CLCN5 206765_at AF153820 −1 KCNJ2 206880_at NM_005446 −1 P2RXL1 207075_at NM_004895 −1 CIAS1 207113_s_at NM_000594 −1 TNF 207287_at NM_025026 −1 FLJ14107 207490_at NM_025019 −1 TUBA4 207535_s_at NM_002502 −1 NFKB2 207574_s_at NM_015675 −1 GADD45B 207850_at NM_002090 −1 CXCL3 207901_at NM_002187 −1 IL12B 207984_s_at NM_005374 −1 MPP2 208025_s_at NM_003483 −1 HMGA2 208039_at NM_003048 −1 NM_003048 208120_x_at NM_031221 −1 — 208455_at NM_002855 −1 PVRL1 208695_s_at BC001019 −1 RPL39 208886_at BC000145 −1 H1F0 208961_s_at AB017493 −1 COPEB 209034_at AF279899 −1 PNRC1 209039_x_at AF001434 −1 EHD1 209124_at U70451 −1 MYD88 209304_x_at AF087853 −1 GADD45B 209305_s_at AF078077 −1 GADD45B 209545_s_at AF027706 −1 RIPK2 209738_x_at M31125 −1 M31125 209774_x_at M57731 −1 CXCL2 209874_x_at AK023066 −1 CNNM2 209939_x_at AF005775 −1 CFLAR 210001_s_at AB005043 −1 SOCS1 210118_s_at M15329 −1 IL1A 210175_at BC000853 −1 C2orf3 210254_at L35848 −1 MS4A3 210275_s_at AF062347 −1 ZA20D2 210414_at AF169675 −1 FLRT1 210592_s_at M55580 −1 SAT 210651_s_at L41939 −1 EPHB2 211307_s_at U43677 −1 FCAR 211332_x_at AF144241 −1 HFE 211403_x_at AF167079 −1 VCX-(C,2,3); VCY 211434_s_at AF015524 −1 CCRL2 211506_s_at AF043337 −1 IL8 211578_s_at M60725 −1 RPS6KB1 211610_at U51869 −1 COPEB 213575_at AW978896 −1 TRA2A 215462_at AI978990 −1 LOC149478 211863_x_at AF079408 −1 HFE 211924_s_at AY029180 −1 PLAUR 211973_at AW341200 −1 NUDT3 212099_at AI263909 −1 RHOB 212291_at AI393355 −1 HIPK1 212602_at AI806395 −1 WDFY3 212657_s_at AW083357 −1 IL1RN 212659_s_at AW083357 −1 IL1RN 213002_at AA770596 −1 AA770596 213038_at AL031602 −1 IBRDC3 213146_at AA521267 −1 JMJD3 213281_at BE327172 −1 BE327172 213593_s_at AW978896 −1 TRA2A 213632_at M94065 −1 DHODH 213675_at W61005 −1 FLJ25106 213676_at AL038824 −1 AW125688 213988_s_at BE971383 −1 SAT 214211_at AA083483 −1 FTH1 214349_at AV764378 −1 ORF2 214421_x_at AV652420 −1 CYP2C9 214637_at BG437034 −1 OSM 214657_s_at AU134977 −1 TncRNA 215006_at AK023816 −1 EZH2 215078_at AL050388 −1 SOD2 215189_at X99142 −1 KRTHB6 215223_s_at W46388 −1 SOD2 215308_at AF052148 −1 G22P1 215485_s_at AA284705 −1 ICAM1 215577_at AU146791 −1 UBE2E1 215758_x_at AC007204 −1 ZNF505 215775_at BF084105 −1 BF084105 215899_at AK022331 −1 AK022331 215987_at AV654984 −1 AV654984 216015_s_at AK027194 −1 CIAS1 216016_at AK027194 −1 CIAS1 216084_at AL080137 −1 LOC389715 216114_at AL049430 −1 NCKIPSD 216153_x_at AK022897 −1 RECK 216243_s_at BE563442 −1 IL1RN 216336_x_at AL031602 −1 AL031602 216366_x_at AF047245 −1 AF047245 216438_s_at AL133228 −1 TMSB4X, TMSL3 216678_at AK000773 −1 AK000773 216774_at AK025325 −1 AK025325 216973_s_at S49765 −1 HOXB7 216997_x_at AL358975 −1 TLE4 217362_x_at AF005487 −1 HLA-DRB6 217415_at M21610 −1 M21610 217489_s_at S72848 −1 IL6R 217741_s_at NM_006007 −1 ZA20D2 217996_at NM_007350 −1 PHLDA1 218177_at NM_020412 −1 CHMP1.5 218198_at NM_018180 −1 DHX32 218611_at NM_016545 −1 IER5 218810_at NM_025079 −1 FLJ23231 219312_s_at NM_023929 −1 ZBTB10 219358_s_at NM_018404 −1 CENTA2 219397_at NM_025147 −1 FLJ13448 219450_at NM_018302 −1 FLJ11017 219617_at NM_024766 −1 FLJ23451 219901_at NM_018351 −1 FGD6 219935_at NM_007038 −1 ADAMTS5 220054_at NM_016584 −1 IL23A 220091_at NM_017585 −1 SLC2A6 220215_at NM_024804 −1 FLJ12606 220712_at NM_024984 −1 NM_024984 220737_at AF184965 −1 AF184965 220740_s_at NM_005135 −1 SLC12A6 220776_at NM_013348 −1 KCNJ14 220924_s_at NM_018976 −1 SLC38A2 221236_s_at NM_030795 −1 STMN4 221323_at NM_025218 −1 ULBP1 221345_at NM_005306 −1 GPR43 221477_s_at BC001980 −1 gasdermin 222136_x_at AK022905 −1 ZNF43 222303_at AV700891 −1 AV700891 222326_at AW973834 −1 AW973834 222329_x_at AW974816 −1 AW974816 36564_at W27419 −1 IBRDC3 37028_at U83981 −1 PPP1R15A 39402_at M15330 −1 IL1B 41386_i_at AB002344 −1 JMJD3 41387_r_at AB002344 −1 JMJD3 200023_s_at AI001896 1 EIF3S5 200028_s_at NM_020151 1 STARD7 200030_s_at NM_002635 1 SLC25A3 200083_at AA621731 1 USP22 200098_s_at T33068 1 ANAPC5 200609_s_at NM_017491 1 WDR1 200625_s_at NM_006367 1 CAP1 200688_at D13642 1 SF3B3 200816_s_at NM_000430 1 PAFAH1B1 200830_at NM_002808 1 PSMD2 200840_at NM_005548 1 KARS 200870_at NM_007178 1 STRAP 200899_s_at AK002091 1 MGEA5 200910_at NM_005998 1 CCT3 200932_s_at NM_006400 1 DCTN2 200961_at NM_012248 1 SEPHS2 201010_s_at NM_006472 1 TXNIP 201027_s_at NM_015904 1 EIF5B 201036_s_at NM_005327 1 HADHSC 201106_at NM_002085 1 GPX4 201174_s_at NM_018975 1 TERF2IP 201229_s_at BC000422 1 ARIH2 201405_s_at NM_006833 1 COPS6 201540_at NM_001449 1 FHL1 201541_s_at NM_006349 1 ZNHIT1 201569_s_at NM_015380 1 CGI-51 201612_at NM_000696 1 ALDH9A1 201672_s_at NM_005151 1 USP14 201688_s_at BG389015 1 TPD52 201689_s_at NM_005079 1 TPD52 202042_at NM_002109 1 HARS 202658_at NM_003846 1 PEX11B 202836_s_at BC001046 1 TXNL4A 204220_at NM_004877 1 GMFG 201805_at NM_002733 1 PRKAG1 201863_at NM_014077 1 FAM32A 201959_s_at AA488899 1 MYCBP2 201964_at N64643 1 N64643 202009_at NM_007284 1 PTK9L 202020_s_at NM_006055 1 LANCL1 202057_at AW051311 1 KPNA1 202116_at NM_006268 1 DPF2 202127_at AB011108 1 PRPF4B 202167_s_at NM_022362 1 MMS19L 202220_at NM_014949 1 KIAA0907 202244_at NM_002796 1 PSMB4 202259_s_at NM_014887 1 PFAAP5 202265_at NM_005180 1 BMI1 202271_at AB007952 1 AB007952 202296_s_at NM_007033 1 RER1 202306_at NM_002696 1 POLR2G 202342_s_at NM_015271 1 TRIM2 202353_s_at NM_002816 1 PSMD12 202365_at BC004815 1 MGC5139 202439_s_at NM_000202 1 IDS 202475_at NM_006326 1 NIFIE14 202529_at NM_002766 1 PRPSAP1 202560_s_at NM_015607 1 DKFZP547E1010 202564_x_at NM_001667 1 ARL2 202568_s_at AI745639 1 MARK3 202759_s_at BE879367 1 PALM2-AKAP2 202761_s_at NM_015180 1 SYNE2 202792_s_at NM_014678 1 KIAA0685 202811_at NM_006463 1 STAMBP 202892_at NM_004661 1 CDC23 202960_s_at NM_000255 1 MUT 202983_at AI760760 1 SMARCA3 203117_s_at NM_014871 1 USP52 203194_s_at NM_005387 1 NUP98 203221_at NM_005077 1 TLE1 203264_s_at NM_015185 1 ARHGEF9 203266_s_at NM_003010 1 MAP2K4 203301_s_at NM_021145 1 DMTF1 203378_at AB020631 1 PCF11 203445_s_at NM_005730 1 CTDSP2 203482_at AL133215 1 C10orf6 203487_s_at NM_015396 1 ARMC8 203517_at NM_006554 1 MTX2 203583_at NM_014044 1 UNC50 203683_s_at NM_003377 1 VEGFB 203710_at NM_002222 1 ITPR1 203721_s_at NM_016001 1 CGI-48 203738_at AI421192 1 FLJ11193 203775_at NM_014251 1 SLC25A13 203804_s_at NM_006107 1 CROP 203865_s_at NM_015833 1 ADARB1 203981_s_at AL574660 1 ABCD4 204000_at NM_016194 1 GNB5 204004_at AI336206 1 PAWR 204060_s_at NM_005044 1 PRKX, PRKY 204139_x_at NM_003422 1 ZNF42 204153_s_at AI738965 1 MFNG 204178_s_at NM_006328 1 RBM14 204185_x_at NM_005038 1 PPID 204202_at NM_017604 1 IQCE 204279_at NM_002800 1 PSMB9 204291_at NM_014803 1 ZNF518 204327_s_at NM_003455 1 ZNF202 204396_s_at NM_005308 1 GRK5 204410_at NM_004681 1 EIF1AY 204510_at NM_003503 1 CDC7 204528_s_at NM_004537 1 NAP1L1 204581_at NM_001771 1 CD22 204593_s_at AA046752 1 FLJ20232 204618_s_at NM_005254 1 GABPB2 204640_s_at NM_003563 1 SPOP 204772_s_at NM_007344 1 TTF1 204848_x_at NM_000559 1 HBG1, HBG2 204873_at NM_000466 1 PEX1 204950_at NM_014959 1 CARD8 205034_at NM_004702 1 CCNE2 205049_s_at NM_001783 1 CD79A 208985_s_at BC002719 1 EIF3S1 209685_s_at M13975 1 PRKCB1 205296_at AL365505 1 RBL1 205297_s_at NM_000626 1 CD79B 205353_s_at NM_002567 1 PBP 205612_at NM_007351 1 MMRN1 205671_s_at NM_002120 1 HLA-DOB 205788_s_at NM_014827 1 NM_014827 205790_at NM_003726 1 SCAP1 205933_at NM_015559 1 SETBP1 206272_at NM_006542 1 SPHAR 206493_at NM_000419 1 ITGA2B 206494_s_at NM_000419 1 ITGA2B 206652_at NM_016384 1 DKFZp779H233 206854_s_at NM_003188 1 MAP3K7 207081_s_at NM_002650 1 PIK4CA 207170_s_at NM_015416 1 LETMD1 207180_s_at NM_006410 1 HTATIP2 207314_x_at NM_006737 1 KIR3DL2 207405_s_at NM_002873 1 RAD17 207522_s_at NM_005173 1 ATP2A3 207655_s_at NM_013314 1 BLNK 207812_s_at NM_015530 1 GORASP2 207830_s_at NM_002713 1 PPP1R8 207842_s_at NM_007359 1 CASC3 208073_x_at NM_003316 1 TTC3 208184_s_at NM_003274 1 TMEM1 208622_s_at AA670344 1 VIL2 208640_at BG292367 1 RAC1 208651_x_at BG327863 1 CD24 208722_s_at BC001081 1 ANAPC5 208752_x_at AI888672 1 NAP1L1 208758_at D89976 1 ATIC 208792_s_at M25915 1 CLU 208809_s_at AL136632 1 C6orf62 208837_at BC000027 1 C15orf22 209007_s_at AF247168 1 NPD014 209058_at AB002282 1 EDF1 209075_s_at AY009128 1 ISCU 209139_s_at AF083033 1 PRKRA 209153_s_at M31523 1 TCF3 209215_at L11669 1 TETRAN 209234_at BF939474 1 KIF1B 209273_s_at BG387555 1 HBLD2 209284_s_at AI922509 1 RAP140 209340_at S73498 1 UAP1 209431_s_at AF254083 1 ZNF278 209447_at AF043290 1 SYNE1 209449_at AF196468 1 LSM2 209452_s_at AF035824 1 VTI1B 209482_at BC001430 1 POP7 209486_at BC004546 1 SAS10 209503_s_at AF035309 1 PSMC5 209549_s_at BC001121 1 DGUOK 209572_s_at AF080227 1 EED 209625_at BC004100 1 PIGH 209630_s_at U87460 1 FBXW2 209659_s_at AF164598 1 CDC16 209729_at BC001782 1 GAS2L1 209771_x_at AA761181 1 CD24 209778_at AF007217 1 TRIP11 209903_s_at U49844 1 ATR 209917_s_at BC002709 1 TP53AP1 210046_s_at U52144 1 IDH2 210356_x_at BC002807 1 MS4A1 210378_s_at BC004118 1 SSNA1 210627_s_at BC002804 1 GCS1 210690_at U96845 1 KLRC4 210715_s_at AF027205 1 SPINT2 210719_s_at BC002552 1 HMG20B 210886_x_at AB007457 1 TP53AP1 210927_x_at BC004239 1 JTB 211036_x_at BC006301 1 ANAPC5 211479_s_at M81778 1 HTR2C 211881_x_at AB014341 1 IGLJ3 213351_s_at AB018322 1 KIAA0779 213364_s_at AI052536 1 SNX1 211784_s_at BC006181 1 SFRS1 211945_s_at BG500301 1 ITGB1 211954_s_at BC000947 1 RANBP5 211979_at AB046844 1 GPR107 212040_at BG249599 1 TGOLN2 212068_s_at AB011087 1 KIAA0515 212114_at BE967207 1 microtubule protein 212121_at BE962354 1 C10orf61 212140_at AB014548 1 SCC-112 212201_at AW274877 1 KIAA0692 212244_at AL050091 1 GRINL1A 212247_at AW008531 1 NUP205 212321_at BE999972 1 BE999972 212326_at AB007922 1 VPS13D 212361_s_at AA805753 1 ATP2A2 212548_s_at BF515124 1 KIAA0826 212559_at AU148827 1 AU148827 212566_at AL523310 1 MAP4 212583_at AB011132 1 AB011132 212611_at AV728526 1 DTX4 212632_at N32035 1 STX7 212655_at AB011151 1 ZCCHC14 212667_at AL575922 1 SPARC 212690_at AB018268 1 DDHD2 212714_at AL050205 1 LOC113251 212750_at AB020630 1 PPP1R16B 212760_at AB002347 1 C6orf133 212813_at AA149644 1 JAM3 212855_at D87466 1 KIAA0276 212955_s_at AL037557 1 POLR2I 213061_s_at AA643304 1 NTAN1 213065_at AB011118 1 MGC23401 213088_s_at BE551340 1 DNAJC9 213090_s_at AI744029 1 TAF4 213106_at AI769688 1 ATP8A1 213165_at AI041204 1 CAP350 213213_at AL035669 1 DATF1 213267_at AL162056 1 KIAA1117 213278_at AW014788 1 MTMR9 213375_s_at N80918 1 CG018 213408_s_at AK024034 1 PIK4CA 213410_at AL050102 1 C10orf137 213460_x_at N29665 1 WBSCR20C 213483_at AK025679 1 KIAA0073 213515_x_at AI133353 1 HBG2 213528_at AL035369 1 MGC9084 213626_at AL049442 1 CBR4 213634_s_at AL031588 1 TRMT1 213653_at AW069290 1 METTL3 213659_at AA209420 1 ZNF75 213672_at AA621558 1 MARS 213838_at AA191426 1 AA191426 214130_s_at AI821791 1 PDE4DIP 214669_x_at BG485135 1 BG485135 214749_s_at AK000818 1 ARMCX6 214948_s_at AL050136 1 TMF1 215158_s_at AK022531 1 DEDD 215227_x_at BG035989 1 ACP1 215318_at AL049782 1 CG012 215343_at AF070587 1 0610010D24Rik 215648_at AU144324 1 KIAA1068 215925_s_at AF283777 1 CD72 216237_s_at AA807529 1 MCM5 216261_at AI151479 1 ITGB3 216338_s_at AK021433 1 C6orf109 218100_s_at NM_018010 1 ESRRBL1 219802_at NM_024854 1 FLJ22028 216379_x_at AK000168 1 CD24 216907_x_at X93596 1 KIR3DL2 216956_s_at AF098114 1 ITGA2B 217043_s_at U95822 1 MFN1 217418_x_at X12530 1 MS4A1 217645_at AW088547 1 AW088547 217730_at NM_022152 1 PP1201 217772_s_at NM_014342 1 MTCH2 217792_at NM_014426 1 SNX5 217815_at NM_007192 1 SUPT16H 217896_s_at NM_024946 1 NIP30 217906_at NM_014315 1 KLHDC2 217908_s_at NM_018442 1 IQWD1 217938_s_at AI743396 1 KCMF1 217978_s_at NM_017582 1 UBE2Q 217979_at NM_014399 1 TM4SF13 217986_s_at AA102574 1 BAZ1A 218004_at NM_018045 1 FLJ10276 218082_s_at NM_014517 1 UBP1 218124_at NM_017750 1 FLJ20296 218132_s_at NM_024075 1 LENG5 218179_s_at NM_021942 1 FLJ12716 218212_s_at NM_004531 1 MOCS2 218220_at NM_021640 1 C12orf10 218237_s_at NM_030674 1 SLC38A1 218250_s_at NM_013354 1 CNOT7 218301_at NM_018226 1 RNPEPL1 218328_at NM_016035 1 COQ4 218339_at NM_014180 1 MRPL22 218361_at NM_018178 1 GPP34R 218371_s_at AA969958 1 PSPC1 218432_at NM_012175 1 FBXO3 218440_at NM_020166 1 MCCC1 218456_at NM_023925 1 C1QDC1 218462_at NM_025065 1 RPF1 218504_at NM_016044 1 FAHD2A 218533_s_at NM_017859 1 UCKL1 218575_at NM_022662 1 ANAPC1 218607_s_at NM_018115 1 SDAD1 218608_at NM_022089 1 HSA9947 218626_at NM_019843 1 EIF4ENIF1 218639_s_at NM_025112 1 MGC11349 218654_s_at NM_016071 1 MRPS33 218667_at NM_022368 1 PJA1 218679_s_at NM_016208 1 VPS28 218771_at NM_018216 1 PANK4 219067_s_at NM_017615 1 C10orf86 219126_at NM_018288 1 PHF10 219151_s_at NM_007081 1 RABL2A, RABL2B 219180_s_at AI817074 1 PEX26 219185_at NM_012241 1 SIRT5 219283_at NM_014158 1 C1GALT2 219292_at NM_018105 1 THAP1 219317_at NM_007195 1 POLI 219470_x_at NM_019084 1 CCNJ 219581_at NM_025265 1 SEN2L 219627_at NM_024910 1 FLJ12700 219822_at NM_004294 1 MTRF1 219880_at NM_022907 1 FLJ23053 219979_s_at NM_016401 1 HSPC138 220044_x_at NM_016424 1 CROP 220059_at NM_012108 1 BRDG1 220169_at NM_024943 1 FLJ23235 220216_at NM_019607 1 FLJ11267 220261_s_at NM_018106 1 ZDHHC4 220387_s_at NM_007071 1 HHLA3 220418_at NM_018961 1 UBASH3A 220936_s_at NM_018267 1 H2AFJ 221208_s_at NM_024631 1 FLJ23342 221253_s_at NM_030810 1 TXNDC5 221476_s_at AF279903 1 RPL15 221515_s_at BC001214 1 LCMT1 221516_s_at BC002587 1 FLJ20232 221548_s_at AY024365 1 ILKAP 221586_s_at U15642 1 E2F5 221736_at BG236163 1 KIAA1219 221791_s_at BG167522 1 HSPC016 221811_at BF033007 1 PERLD1 221932_s_at AA133341 1 C14orf87 222111_at AU145293 1 KIAA1164 222130_s_at AK024635 1 FTSJ2 222155_s_at AK021918 1 GPR172A 222233_s_at AK022922 1 DCLRE1C 222273_at AI419423 1 AI419423 266_s_at L33930 1 CD24 32259_at AB002386 1 EZH1 33307_at AL022316 1 CGI-96 37965_at AA181053 1 PARVB 37966_at AA187563 1 PARVB 38043_at X55448 1 FAM3A 45828_at AI768100 1 FLJ10241 48825_at AA887083 1 ING4 50374_at AA150503 1 LOC339229 52164_at AA065185 1 C11orf24 64432_at W05463 1 FLJ39616 65472_at AI161338 1 AI161338 Table 1: Provided are genetic markers which are differentially expressed between subjects diagnosed with probable multiple sclerosis and healthy controls (the Probeset ID of the Affymetrix Gene Chip), along with the corresponding GenBank accession number (GenBank Acc. No.), the gene symbol and the direction (Dir) of change in gene expression (“1”- upregulation; “−1” - downregulation). Note that the p values of the TNOM, Info and t-Test statistical tests all passed the 95% confidence level.

Independent verification by support vector machine (SVM)—Verification of the probable PBMC gene expression signature (554 genes) was performed on an independent group of 15 subjects (12 patients, 3 controls) by SVM analysis and resulted in high classification rate of 80%. These findings suggest that the identified gene expression signature in probable MS is reliable and not related to spurious difference due to multiple testing.

Example 2 Gene Expression Analysis of Subjects Whose Diagnosis Converted to Definite MS or Sustained Probable MS

Experimental Results

Conversion to definite MS—2-year results—During the follow up period of 2 year, 30% of patients (12/40) experienced a second attack and progressed to definite MS disease (defined as early convectors to definite MS). Comparison of the gene expression pattern of only these probable patients who further experienced a second attack and therefore defined as definite MS (12 patients) (using the blood cell samples obtained when the subjects were defined as probable multiple sclerosis, i.e., after the first neurological attack) to matched control group (11 subjects) identified 1517 most informative genes (Table 2, hereinbelow and FIG. 2 a), all passed FDR at p<0.03 and 8 genes—Bonfferoni correction at p<3.2×10⁻⁵. PCA performed on these 1517 most informative genes demonstrated correct classification rate with no errors (FIG. 2 b).

TABLE 2 Differentially expressed markers between probable multiple sclerosis subjects which further developed definite multiple sclerosis and healthy controls GenBank Probeset Acc. No. Dir Gene Symbol 214376_at AI263044 −1 AI263044 217446_x_at AL080160 −1 AL080160 215185_at AK024177 −1 AK024177 217449_at AL137284 −1 DKFZp434D1516 221877_at BF508835 −1 FKSG27 222135_at AK022663 −1 KIAA1956 217381_s_at X69383 −1 T-cell receptor gamma 221477_s_at BC001980 −1 NP_079012.2 215995_x_at AU147598 −1 LOC283585 214826_at U79276 −1 2′-PDE 44702_at R77097 −1 7h3 201269_s_at AB028991 −1 AB028991 214979_at AK000791 −1 ABCC3 205566_at NM_007011 −1 ABHD2 207268_x_at NM_005759 −1 ABI2 217024_x_at AC004832 −1 AC004832 206776_x_at NM_001612 −1 ACRV1 207973_x_at NM_020110 −1 ACRV1 207990_x_at NM_020114 −1 ACRV1 207991_x_at NM_020113 −1 ACRV1 211489_at D32201 −1 ADRA1A 38447_at U08438 −1 ADRBK1 201205_at AF006751 −1 AF006751 216366_x_at AF047245 −1 AF047245 211189_x_at AF054816 −1 AF054816 215837_x_at AF113018 −1 AF113018 208849_at AF118091 −1 AF118091 219558_at NM_024524 −1 AFURS1 205357_s_at NM_000685 −1 AGTR1 207464_at NM_014121 −1 AHCYL1 214139_at AI051476 −1 AI051476 221960_s_at AI189609 −1 AI189609 214379_at AI954458 −1 AI954458 216678_at AK000773 −1 AK000773 216682_s_at AK021457 −1 AK021457 216051_x_at AK022045 −1 AK022045 217335_at AK023539 −1 AK023539 216739_at AK024527 −1 AK024527 216746_at AK024606 −1 AK024606 216437_at AK024949 −1 AK024949 215405_at AK025072 −1 AK025072 216774_at AK025325 −1 AK025325 217218_at AK027005 −1 AK027005 210517_s_at AB003476 −1 AKAP12 205359_at NM_004274 −1 AKAP6 211172_x_at AF161075 −1 AKAP7 204151_x_at NM_001353 −1 AKR1C1 216336_x_at AL031602 −1 AL031602 41856_at AL049370 −1 AL049370 216499_at AL137590 −1 AL137590 216828_at AL441988 −1 AL441988 210544_s_at BC002430 −1 ALDH3A2 214423_x_at AV652403 −1 ALDOB 207755_at NM_025017 −1 AMOTL2 213001_at AF007150 −1 ANGPTL2 218418_s_at NM_015493 −1 ANKRD25 203074_at NM_001630 −1 ANXA8 211553_x_at AF149794 −1 APAF1 206350_at NM_001639 −1 APCS 202914_s_at NM_014784 −1 ARHGEF11 207919_at NM_004314 −1 ART1 202672_s_at NM_001674 −1 ATF3 216070_at AL049331 −1 ATP1B1 214132_at BG232034 −1 ATP5C1 204624_at NM_000053 −1 ATP7B 222303_at AV700891 −1 AV700891 206251_s_at NM_000706 −1 AVPR1A 212999_x_at AW276186 −1 AW276186 222363_at AW979018 −1 AW979018 219326_s_at AF288208 −1 B3GNT1 209413_at BC002431 −1 B4GALT2 91920_at AI205180 −1 BCAN 219444_at NM_021946 −1 BCORL1 213281_at BE327172 −1 BE327172 221917_s_at BF058465 −1 BF058465 213561_at BF062335 −1 BF062335 215775_at BF084105 −1 BF084105 212002_at BG171020 −1 BG171020 220580_at NM_025044 −1 BICC1 218955_at NM_018310 −1 BRF2 201235_s_at BG339064 −1 BTG2 215072_x_at AK025270 −1 C10orf137 43934_at AA479495 −1 C11ORF4 219720_s_at NM_017972 −1 C14orf118 215219_at AK025095 −1 C21orf5 48030_i_at H93077 −1 C5orf4 220231_at NM_006658 −1 C7orf16 61874_at AL042496 −1 C9orf7 205949_at M33987 −1 CA1 205199_at NM_001216 −1 CA9 214845_s_at AF257659 −1 CALU 34846_at AF112472 −1 CAMK2B 210787_s_at AF140507 −1 CAMKK2 205114_s_at NM_002983 −1 CCL3, CCL3L1, MGC12815 202705_at NM_004701 −1 CCNB2 205098_at AI421071 −1 CCR1 208304_at NM_001837 −1 CCR3 207445_s_at AF145439 −1 CCR9 210325_at M28825 −1 CD1A 207176_s_at NM_005191 −1 CD80 211190_x_at AF054817 −1 CD84 209287_s_at AI754416 −1 CDC42EP3 209057_x_at AB007892 −1 CDC5L 220115_s_at NM_006727 −1 CDH10 211804_s_at AB012305 −1 CDK2 211883_x_at M76742 −1 CEACAM1 40020_at AB011536 −1 CELSR3 220885_s_at NM_018451 −1 CENPJ 202938_x_at NM_015703 −1 CGI-96, dJ222E13.2 207486_x_at NM_004067 −1 CHN2 206635_at NM_000748 −1 CHRNB2 215916_at AL157418 −1 CHRNE 207075_at NM_004895 −1 CIAS1 216016_at AK027194 −1 CIAS1 206818_s_at NM_017649 −1 CNNM2 209874_x_at AK023066 −1 CNNM2 206586_at NM_001841 −1 CNR2 211980_at AI922605 −1 COL4A1 216898_s_at U02520 −1 COL4A3 52651_at AI806793 −1 COL8A2 205624_at NM_001870 −1 CPA3 222301_at BF530257 −1 CROC4 202468_s_at NM_003798 −1 CTNNAL1 219080_s_at NM_019857 −1 CTPS2 206297_at NM_007272 −1 CTRC 205927_s_at NM_001910 −1 CTSE 206775_at NM_001081 −1 CUBN 204470_at NM_001511 −1 CXCL1 209774_x_at M57731 −1 CXCL2 207850_at NM_002090 −1 CXCL3 206336_at NM_002993 −1 CXCL6 205088_at NM_005491 −1 CXorf6 214610_at AV702430 −1 CYP11B1 217558_at BE971373 −1 CYP2C9 213873_at D29810 −1 D29810 217025_s_at AL110225 −1 DBN1 219490_s_at NM_022836 −1 DCLRE1B 205338_s_at NM_001922 −1 DCT 213632_at M94065 −1 DHODH 219799_s_at NM_005771 −1 DHRS9 204494_s_at AW516789 −1 DKFZP434H132 214699_x_at AK024279 −1 DKFZP434J154 219872_at NM_016613 −1 DKFZp434L142 78495_at R61320 −1 DKFZp762P2111 208216_at NM_001934 −1 DLX4 33768_at L19267 −1 DMWD 202866_at BG283782 −1 DNAJB12 219746_at NM_012074 −1 DPF3 206590_x_at NM_016574 −1 DRD2 216938_x_at S69899 −1 DRD2 211541_s_at U52373 −1 DYRK1A 218660_at NM_003494 −1 DYSF 203692_s_at AI640363 −1 E2F3 208112_x_at NM_006795 −1 EHD1 209038_s_at AL579035 −1 EHD1 209039_x_at AF001434 −1 EHD1 210376_x_at M25269 −1 ELK1 205994_at NM_001973 −1 ELK4 396_f_at X97671 −1 EPOR 206794_at NM_005235 −1 ERBB4 205225_at NM_000125 −1 ESR1 206501_x_at NM_004956 −1 ETV1 215006_at AK023816 −1 EZH2 205189_s_at NM_000136 −1 FANCC 204819_at NM_004463 −1 FGD1 219901_at NM_018351 −1 FGD6 208417_at NM_020996 −1 FGF6 219389_at NM_017982 −1 FLJ10052 219501_at NM_017993 −1 FLJ10094 218815_s_at NM_018022 −1 FLJ10199 218814_s_at NM_018252 −1 FLJ10874 219450_at NM_018302 −1 FLJ11017 220465_at NM_024988 −1 FLJ12355 220578_at NM_025008 −1 FLJ13544 220149_at NM_024861 −1 FLJ22671 221224_s_at NM_024819 −1 FLJ22955 215062_at AL390143 −1 FMNL2 206263_at NM_002022 −1 FMO4 202768_at NM_006732 −1 FOSB 219889_at NM_005479 −1 FRAT1 211628_x_at J04755 −1 FTHP1 215744_at AW514140 −1 FUS 209893_s_at M58596 −1 FUT4 202488_s_at NM_005971 −1 FXYD3 204452_s_at AF072872 −1 FZD1 213524_s_at NM_015714 −1 G0S2 214772_at H08993 −1 G2 208217_at NM_002043 −1 GABRR2 207574_s_at NM_015675 −1 GADD45B 209305_s_at AF078077 −1 GADD45B 207357_s_at NM_017540 −1 GALNT10 220929_at NM_017417 −1 GALNT8 207954_at NM_002050 −1 GATA2 209710_at AL563460 −1 GATA2 210358_x_at BC002557 −1 GATA2 221314_at NM_005260 −1 GDF9 205100_at NM_005110 −1 GFPT2 211815_s_at AF219138 −1 GGA3 207131_x_at NM_013430 −1 GGT1 208284_x_at NM_013421 −1 GGT1 209919_x_at L20490 −1 GGT1 211417_x_at L20493 −1 GGT1 215977_x_at X68285 −1 GK 207034_s_at NM_030379 −1 GLI2 204762_s_at NM_020988 −1 GNAO1 209220_at L47125 −1 GPC3 206264_at L11702 −1 GPLD1 209168_at AW148844 −1 GPM6B 211977_at AK024651 −1 GPR107 205220_at NM_006018 −1 GPR109B 221394_at NM_014626 −1 GPR58 214655_at U18549 −1 GPR6 220481_at NM_006794 −1 GPR75 205276_s_at U87964 −1 GTPBP1 44783_s_at R61374 −1 HEY1 210864_x_at AF144240 −1 HFE 211328_x_at AF144244 −1 HFE 211329_x_at AF115264 −1 HFE 211332_x_at AF144241 −1 HFE 211863_x_at AF079408 −1 HFE 205425_at NM_005338 −1 HIP1 205426_s_at NM_005338 −1 HIP1 209398_at BC002649 −1 HIST1H1C 214290_s_at AI313324 −1 HIST2H2AA 218280_x_at BC001629 −1 HIST2H2AA 208812_x_at BC004489 −1 HLA-C, HLA-B 211911_x_at L07950 −1 HLA-C, HLA-B 211654_x_at M17565 −1 HLA-DQB1 211528_x_at M90685 −1 HLA-G 211529_x_at M90684 −1 HLA-G 213844_at NM_019102 −1 HOXA5 205601_s_at NM_002147 −1 HOXB5 216973_s_at S49765 −1 HOXB7 204221_x_at U16307 −1 HRB2 214085_x_at AI912583 −1 HRB2 209192_x_at BC000166 −1 HTATIP 207404_s_at NM_000865 −1 HTR1E 36564_at W27419 −1 IBRDC3 202637_s_at AI608725 −1 ICAM1 202638_s_at NM_000201 −1 ICAM1 215485_s_at AA284705 −1 ICAM1 203328_x_at NM_004969 −1 IDE 202081_at NM_004907 −1 IER2 201631_s_at NM_003897 −1 IER3 208261_x_at NM_002171 −1 IFNA10 214569_at NM_002169 −1 IFNA5 208548_at NM_021002 −1 IFNA6 208441_at NM_015883 −1 IGF1R 202421_at AB007935 −1 IGSF3 209032_s_at AF132811 −1 IGSF4 207901_at NM_002187 −1 IL12B 64440_at AI560217 −1 IL17RC 206295_at NM_001562 −1 IL18 205067_at NM_000576 −1 IL1B 39402_at M15330 −1 IL1B 212659_s_at AW083357 −1 IL1RN 216243_s_at BE563442 −1 IL1RN 220056_at NM_021258 −1 IL22RA1 202859_x_at NM_000584 −1 IL8 211506_s_at AF043337 −1 IL8 202531_at NM_002198 −1 IRF1 206766_at AF112345 −1 ITGA10 37201_at D38535 −1 ITIH4 203682_s_at NM_002225 −1 IVD 209098_s_at U73936 −1 JAG1 201465_s_at BC002646 −1 JUN 211806_s_at D87291 −1 KCNJ15 58916_at AI672101 −1 KCTD14 211028_s_at BC006233 −1 KHK 216251_s_at BF965437 −1 KIAA0153 210954_s_at AF201292 −1 KIAA0669 31826_at AB014574 −1 KIAA0674 212054_x_at AK026096 −1 KIAA0676 213358_at AB018345 −1 KIAA0802 207705_s_at NM_025176 −1 KIAA0980 213478_at AB028949 −1 KIAA1026 216294_s_at AL137254 −1 KIAA1109 221078_s_at NM_018084 −1 KIAA1212 222367_at AI921841 −1 KIAA1971, LOC339005 205318_at NM_004984 −1 KIF5A 207908_at NM_000423 −1 KRT2A 215189_at X99142 −1 KRTHB6 221717_at L25664 −1 L25664 219813_at NM_004690 −1 LATS1 204012_s_at AL529189 −1 LCMT2 215462_at AI978990 −1 LOC149478 51774_s_at AW014299 −1 LOC222070 58900_at AW025284 −1 LOC222070 217520_x_at BG396614 −1 LOC283683 213751_at AW873594 −1 LOC284352 214838_at AL035297 −1 LOC375035 219071_x_at NM_016458 −1 LOC51236 221629_x_at AF151022 −1 LOC51236 220244_at NM_013343 −1 LOH3CR2A 34697_at AF074264 −1 LRP6 219886_at NM_024548 −1 LRRIQ2 204682_at NM_000428 −1 LTBP2 202018_s_at NM_002343 −1 LTF 209480_at M16276 −1 M16276 209738_x_at M31125 −1 M31125 211241_at M62895 −1 M62895 217920_at BE543064 −1 MAN1A2 209951_s_at AF006689 −1 MAP2K7 214969_at AF251442 −1 MAP3K9 204813_at U34819 −1 MAPK10 201668_x_at AW163148 −1 MARCKS 202485_s_at NM_003927 −1 MBD2 200797_s_at AI275690 −1 MCL1 202618_s_at L37298 −1 MECP2 206028_s_at NM_006343 −1 MERTK 211913_s_at L08961 −1 MERTK 211599_x_at U19348 −1 MET 209758_s_at U37283 −1 MFAP5 211717_at BC005853 −1 MGC15396 212340_at BE673723 −1 MGC21416 217548_at AA491625 −1 MGC61550 205905_s_at NM_000247 −1 MICA, MICB 208384_s_at NM_012216 −1 MID2 212021_s_at AU132185 −1 MKI67 218211_s_at NM_024101 −1 MLPH 160020_at Z48481 −1 MMP14 203936_s_at NM_004994 −1 MMP9 203949_at NM_000250 −1 MPO 206186_at NM_001932 −1 MPP3 210594_x_at AF239756 −1 MPZL1 210223_s_at AF031469 −1 MR1 210224_at AF031469 −1 MR1 210242_x_at AF249277 −1 MTHFS 212093_s_at AI695017 −1 MTUS1 207847_s_at NM_002456 −1 MUC1 212365_at BF215996 −1 MYO1B 33197_at U39226 −1 MYO7A 210048_at BC001889 −1 NAPG 218742_at NM_022493 −1 NARFL 217045_x_at AL136967 −1 NCR2 202150_s_at U64317 −1 NEDD9 203927_at NM_004556 −1 NFKBIE 207986_x_at NM_001915 −1 NM_001915 208039_at NM_003048 −1 NM_003048 208180_s_at NM_003543 −1 NM_003543 220814_at NM_017964 −1 NM_017964 221105_at NM_018395 −1 NM_018395 220872_at NM_018547 −1 NM_018547 208540_x_at NM_021039 −1 NM_021039 219680_at NM_024618 −1 NOD9 39548_at U77970 −1 NPAS2 210730_s_at U36269 −1 NPY2R 202340_x_at NM_002135 −1 NR4A1 204105_s_at NM_005010 −1 NRCAM 216959_x_at U55258 −1 NRCAM 210022_at BC004952 −1 NSPC1 217377_x_at AF041811 −1 NTRK3 206553_at NM_002535 −1 OAS2 205660_at NM_003733 −1 OASL 214485_at NM_024410 −1 ODF1 219105_x_at NM_014321 −1 ORC6L 205729_at NM_003999 −1 OSMR 205815_at NM_002580 −1 PAP 213332_at AL031290 −1 PAPPA2 204752_x_at NM_005484 −1 PARP2 215773_x_at AJ236912 −1 PARP2 215418_at AK022316 −1 PARVA 121_at X69699 −1 PAX8 205656_at NM_014459 −1 PCDH17 211066_x_at BC006439 −1 PDGHGA1-12 PDGHGB1-7 206388_at U36798 −1 PDE3A 216061_x_at AK022920 −1 PDGFB 220236_at NM_017990 −1 PDPR 220944_at NM_020393 −1 PGLYRP4 215622_x_at AL137671 −1 PHF7 209346_s_at AL561930 −1 PI4KII 215832_x_at AV722190 −1 PICALM 210256_s_at U78576 −1 PIP5K1A 204267_x_at NM_004203 −1 PKMYT1 202924_s_at AF006005 −1 PLAGL2 202925_s_at NM_002657 −1 PLAGL2 203471_s_at NM_002664 −1 PLEK 39854_r_at AF055000 −1 PNPLA2 206654_s_at NM_006467 −1 POLR3G 210809_s_at D13665 −1 POSTN 207725_at NM_004575 −1 POU4F2 216330_s_at L14482 −1 POU6F1 212226_s_at AA628586 −1 PPAP2B 210235_s_at U22815 −1 PPFIA1 201489_at BC005020 −1 PPIF 201490_s_at NM_005729 −1 PPIF 202014_at NM_014330 −1 PPP1R15A 37028_at U83981 −1 PPP1R15A 221088_s_at NM_017650 −1 PPP1R9A 204506_at AL544951 −1 PPP3R1 210499_s_at AB041834 −1 PQBP1 209766_at AF118073 −1 PRDX3 219732_at NM_017753 −1 PRG-3 217269_s_at AP001672 −1 PRSS7 210195_s_at M34715 −1 PSG1 204897_at AA897516 −1 PTGER4 204748_at NM_000963 −1 PTGS2 202895_s_at D86043 −1 PTPNS1 206157_at NM_002852 −1 PTX3 202148_s_at NM_006907 −1 PYCR1 211471_s_at AF133588 −1 RAB36 37793_r_at AF034956 −1 RAD51L3 204916_at NM_005855 −1 RAMP1 217020_at X04014 −1 RARB 215688_at AL359931 −1 RASGRF1 205115_s_at NM_016196 −1 RBM19 215761_at AK000156 −1 RC3 216153_x_at AK022897 −1 RECK 205879_x_at BC004257 −1 RET 207936_x_at NM_006604 −1 RFPL3 209637_s_at AF030111 −1 RGS12 209545_s_at AF027706 −1 RIPK2 221287_at NM_021133 −1 RNASEL 208270_s_at NM_020216 −1 RNPEP 218441_s_at NM_015540 −1 RPAP1 213223_at AK025866 −1 RPL28 211180_x_at D89788 −1 RUNX1 205485_at NM_000540 −1 RYR1 217033_x_at S76475 −1 S76475 210593_at M55580 −1 SAT 217331_at U63542 −1 SCC-112 59705_at AA911739 −1 SCLY 207413_s_at NM_000335 −1 SCN5A 203788_s_at AI962897 −1 SEMA3C 35666_at U38276 −1 SEMA3F 218122_s_at NM_021627 −1 SENP2 209722_s_at BC002538 −1 SERPINB9 214197_s_at AI762193 −1 SETDB1 33323_r_at X57348 −1 SFN 204051_s_at NM_003014 −1 SFRP4 201742_x_at M69040 −1 SFRS1 37004_at J02761 −1 SFTPB 201739_at NM_005627 −1 SGK 211211_x_at AF100542 −1 SH2D1A 210796_x_at D86359 −1 SIGLEC6 207250_at NM_007374 −1 SIX6 207095_at NM_000452 −1 SLC10A2 217473_x_at AF229163 −1 SLC11A1 203125_x_at AF046997 −1 SLC11A2 202236_s_at NM_003051 −1 SLC16A1 204230_s_at NM_020309 −1 SLC17A7 208389_s_at NM_004171 −1 SLC1A2 207408_at NM_004803 −1 SLC22A14 219344_at NM_018344 −1 SLC29A3 216236_s_at AL110298 −1 SLC2A3 219991_at NM_020041 −1 SLC2A9 210739_x_at AF069510 −1 SLC4A4 211123_at D87920 −1 SLC5A5 205920_at NM_003043 −1 SLC6A6 216092_s_at AL365347 −1 SLC7A8 207499_x_at NM_017979 −1 SMAP-1 214708_at BG484314 −1 SNTB1 215366_at AL353943 −1 SNX13 205482_x_at NM_013306 −1 SNX15 206663_at NM_003112 −1 SP4 205406_s_at NM_017425 −1 SPA17 206239_s_at NM_003122 −1 SPINK1 216981_x_at X60502 −1 SPN 219677_at NM_025106 −1 SSB1 203019_x_at NM_014021 −1 SSX2IP 214441_at NM_005819 −1 STX6 204287_at NM_004711 −1 SYNGR1 203999_at AV731490 −1 SYT1 212679_at AK026529 −1 TBL2 206838_at NM_005149 −1 TBX19 211590_x_at U11271 −1 TBXA2R 205513_at NM_001062 −1 TCN1 221473_x_at U49188 −1 TDE1 215902_at AF009267 −1 TEB4 204653_at BF343007 −1 TFAP2A 205016_at NM_003236 −1 TGFA 203834_s_at NM_006464 −1 TGOLN2 204064_at NM_005131 −1 THOC1 203167_at NM_003255 −1 TIMP2 210176_at AL050262 −1 TLR1 206271_at NM_003265 −1 TLR3 214657_s_at AU134977 −1 TncRNA 207113_s_at NM_000594 −1 TNF 206025_s_at AW188198 −1 TNFAIP6 209294_x_at BC001281 −1 TNFRSF10B 210405_x_at AF153687 −1 TNFRSF10B 206729_at NM_001243 −1 TNFRSF8 211333_s_at AF288573 −1 TNFSF6 206990_at NM_003285 −1 TNR 202807_s_at NM_005488 −1 TOM1 204946_s_at NM_004618 −1 TOP3A 215781_s_at D87012 −1 TOP3B 211943_x_at AL565449 −1 TPT1 36742_at U34249 −1 TRIM15 206911_at NM_005082 −1 TRIM25 208178_x_at NM_007118 −1 TRIO 208349_at NM_007332 −1 TRPA1 214205_x_at AK022131 −1 TXNL2 210803_at AF201385 −1 TXNRD2 215511_at U19345 −1 U19345 209947_at BC003170 −1 UBAP2L 220422_at NM_017481 −1 UBQLN3 221323_at NM_025218 −1 ULBP1 205536_at NM_003371 −1 VAV2 210513_s_at AF091352 −1 VEGF 209822_s_at L22431 −1 VLDLR 204787_at NM_007268 −1 VSIG4 38964_r_at U12707 −1 WAS 221927_s_at AI923458 −1 WBSCR21 71933_at AI218134 −1 WNT6 210200_at BC000108 −1 WWP2 206365_at NM_002995 −1 XCL1 216809_at Z22780 −1 Z22780 201531_at NM_003407 −1 ZFP36 212892_at AW130128 −1 ZNF282 216692_at AL137428 −1 ZNF337 219089_s_at NM_024327 −1 ZNF576 215376_at AU147830 1 MAMMA1001818 212829_at BE878277 1 OVARC1000964 213686_at AI186145 1 AI186145 215287_at AA975427 1 ELISC-1 213750_at AA928506 1 YH77E09 217529_at BE547674 1 LOC402578 215343_at AF070587 1 0610010D24Rik 212114_at BE967207 1 microtubule proteins 212413_at D50918 1 6-Sep 212414_s_at D50918 1 6-Sep 213970_at AA744682 1 AA744682 209307_at AB014540 1 AB014540 207819_s_at NM_000443 1 ABCB4 209620_s_at AB005289 1 ABCB7 214274_s_at AI860341 1 ACAA1 205355_at NM_001609 1 ACADSB 219962_at NM_021804 1 ACE2 201715_s_at NM_014977 1 ACIN1 215227_x_at BG035989 1 ACP1 202135_s_at NM_005735 1 ACTR1B 205260_s_at NM_001107 1 ACYP1 206833_s_at NM_001108 1 ACYP2 208268_at NM_021777 1 ADAM28 209321_s_at AF033861 1 ADCY3 208030_s_at NM_001119 1 ADD1 201773_at NM_015339 1 ADNP 201281_at NM_007002 1 ADRM1 202144_s_at NM_000026 1 ADSL 217729_s_at NM_001130 1 AES 216609_at AF065241 1 AF065241 211071_s_at BC006471 1 AF1Q 210111_s_at AF277175 1 AF277175 204333_s_at NM_000027 1 AGA 203566_s_at NM_000645 1 AGL 200850_s_at NM_006621 1 AHCYL1 202820_at NM_001621 1 AHR 212980_at AL050376 1 AHSA2 204057_at AI073984 1 AI073984 212543_at U83115 1 AIM1 214102_at AK023737 1 AK023737 201675_at NM_003488 1 AKAP1 218580_x_at NM_017900 1 AKIP 202139_at NM_003689 1 AKR7A2 215307_at AL109722 1 AL109722 216421_at AL121886 1 AL121886 216490_x_at AL133267 1 AL133267 201612_at NM_000696 1 ALDH9A1 218203_at NM_013338 1 ALG5 203545_at NM_024079 1 ALG8 214220_s_at AW003635 1 ALMS1 204976_s_at AK023637 1 AMMECR1 208722_s_at BC001081 1 ANAPC5 218769_s_at NM_023039 1 ANKRA2 218093_s_at NM_017664 1 ANKRD10 212211_at AI986295 1 ANKRD17 202442_at NM_001284 1 AP3S1 210278_s_at AF155159 1 AP4S1 213115_at AL031177 1 APG4A 202512_s_at AK001899 1 APG5L 202630_at AA046411 1 APPBP2 213892_s_at AA927724 1 APRT 201526_at NM_001662 1 ARF5 218870_at NM_018460 1 ARHGAP15 213039_at AB011093 1 ARHGEF18 218964_at NM_006465 1 ARID3B 221230_s_at NM_016374 1 ARID4B 201229_s_at BC000422 1 ARIH2 201230_s_at NM_006321 1 ARIH2 218868_at NM_020445 1 ARP3BETA 215457_at AF070647 1 ARPC1A 207988_s_at NM_005731 1 ARPC2 213513_x_at BG034239 1 ARPC2 215684_s_at AL096741 1 ASCC2 212672_at U82828 1 ATM 211755_s_at BC005960 1 ATP5F1 207508_at NM_001689 1 ATP5G3 209492_x_at BC003679 1 ATP5I 202325_s_at NM_001685 1 ATP5J 200818_at NM_001697 1 ATP5O 214934_at AW411030 1 ATP9B 209903_s_at U49844 1 ATR 208833_s_at AF119662 1 ATXN10 214691_x_at AU121431 1 AU121431 222297_x_at AV738806 1 AV738806 221589_s_at AW612403 1 AW612403 202387_at NM_004323 1 BAG1 219667_s_at NM_017935 1 BANK1 202326_at NM_006709 1 BAT8 211833_s_at U19599 1 BAX 200837_at NM_005745 1 BCAP31 210347_s_at AF080216 1 BCL11A 219497_s_at NM_018014 1 BCL11A 202315_s_at NM_004327 1 BCR 213282_at BE501952 1 BE501952 213637_at BE503392 1 BE503392 215440_s_at AL523320 1 BEXL1 222026_at BF437591 1 BF437591 221847_at BF665706 1 BF665706 206255_at NM_001715 1 BLK 207655_s_at NM_013314 1 BLNK 201849_at NM_004052 1 BNIP3 212563_at BG491842 1 BOP1 203502_at NM_001724 1 BPGM 213473_at AL042733 1 BRAP 204531_s_at NM_007295 1 BRCA1 220059_at NM_012108 1 BRDG1 219177_at NM_018321 1 BRIX 201458_s_at NM_004725 1 BUB3 209974_s_at AF047473 1 BUB3 202808_at AK000161 1 C10orf26 55662_at H27225 1 C10orf76 219067_s_at NM_017615 1 C10orf86 218213_s_at NM_014206 1 C11orf10 52164_at AA065185 1 C11orf24 218220_at NM_021640 1 C12orf10 44790_s_at AI129310 1 C13orf18 218940_at NM_024558 1 C14orf138 217768_at NM_016039 1 C14orf166 221932_s_at AA133341 1 C14orf87 201685_s_at NM_014828 1 C14orf92 208837_at BC000027 1 C15orf22 219439_at NM_020156 1 C1GALT1 212164_at AL522296 1 C1orf37 203960_s_at NM_016126 1 C1orf41 214214_s_at AU151801 1 C1QBP 209422_at AY027523 1 C20orf104 218448_at NM_017896 1 C20orf11 219443_at NM_017714 1 C20orf13 217737_x_at NM_016407 1 C20orf43 217851_s_at NM_016045 1 C20orf45 218859_s_at NM_016649 1 C20orf6 202217_at NM_004649 1 C21orf33 218123_at NM_017835 1 C21orf59 221211_s_at NM_020152 1 C21orf7 218037_at NM_024293 1 C2orf17 221984_s_at AL040896 1 C2orf17 219137_s_at NM_020194 1 C2orf33 218518_at NM_016603 1 C5orf5 212176_at AA902326 1 C6orf111 208809_s_at AL136632 1 C6orf62 203259_s_at BC001671 1 C6orf74 41047_at AI885170 1 C9orf16 218992_at NM_018465 1 C9orf46 211984_at AI653730 1 CALM1 200622_x_at AV685208 1 CALM3 203538_at NM_001745 1 CAMLG 218929_at NM_017632 1 CARF 202402_s_at NM_001751 1 CARS 213373_s_at BF439983 1 CASP8 200037_s_at NM_016587 1 CBX3 219174_at NM_025103 1 CCDC2 219470_x_at NM_019084 1 CCNJ 204645_at NM_001241 1 CCNT2 200910_at NM_005998 1 CCT3 200812_at NM_006429 1 CCT7 206398_s_at NM_001770 1 CD19 209583_s_at AF063591 1 CD200 204581_at NM_001771 1 CD22 38521_at X59350 1 CD22 208650_s_at BG327863 1 CD24 208651_x_at BG327863 1 CD24 209771_x_at AA761181 1 CD24 216379_x_at AK000168 1 CD24 203593_at NM_012120 1 CD2AP 213856_at BG230614 1 CD47 200984_s_at X16447 1 CD59 200985_s_at NM_000611 1 CD59 215925_s_at AF283777 1 CD72 205049_s_at NM_001783 1 CD79A 205297_s_at NM_000626 1 CD79B 206761_at NM_005816 1 CD96 205288_at NM_003672 1 CDC14A 203468_at NM_003674 1 CDK10 212899_at AB028951 1 CDK11 204252_at M68520 1 CDK2 34210_at N90866 1 CDW52 218592_s_at NM_017829 1 CECR5 205642_at NM_007018 1 CEP1 209194_at BC005334 1 CETN2 215318_at AL049782 1 CG012 218628_at NM_016053 1 CGI-116 219030_at NM_016058 1 CGI-121 218102_at NM_015954 1 CGI-26 219590_x_at NM_015958 1 CGI-30 203721_s_at NM_016001 1 CGI-48 201569_s_at NM_015380 1 CGI-51 218642_s_at NM_024300 1 CHCHD7 208968_s_at BC002568 1 CIAPIN1 200999_s_at NM_006825 1 CKAP4 201897_s_at BC001425 1 CKS1B 212752_at AA176798 1 CLASP1 219859_at NM_014358 1 CLECSF9 204085_s_at NM_006493 1 CLN5 204577_s_at NM_024793 1 CLUAP1 218111_s_at NM_018686 1 CMAS 208912_s_at BC001362 1 CNP 203642_s_at NM_014900 1 COBLL1 203073_at NM_007357 1 COG2 213243_at AI052003 1 COH1 201652_at NM_006837 1 COPS5 218328_at NM_016035 1 COQ4 200086_s_at AA854966 1 COX4I1 203663_s_at NM_004255 1 COX5A 211025_x_at BC006229 1 COX5B 201754_at NM_004374 1 COX6C 213846_at AA382702 1 COX7C 218142_s_at NM_016302 1 CRBN 208670_s_at AF109873 1 CRI1 205081_at NM_001311 1 CRIP1 204349_at BC005250 1 CRSP9 220753_s_at NM_015974 1 CRYL1 221139_s_at NM_015989 1 CSAD 201160_s_at AL556190 1 CSDA 212073_at AI631874 1 CSNK2A1 203575_at NM_001896 1 CSNK2A2 213980_s_at AA053830 1 CTBP1 221742_at AI472139 1 CUGBP1 201372_s_at AU145232 1 CUL3 218970_s_at NM_015960 1 CUTC 214974_x_at AK026546 1 CXCL5 215726_s_at M22976 1 CYB5 220999_s_at NM_030778 1 CYFIP2 221905_at BF516433 1 CYLD 207786_at NM_024514 1 CYP2R1 216060_s_at AK021890 1 DAAM1 201624_at NM_001349 1 DARS 218443_s_at NM_018959 1 DAZAP1 202428_x_at NM_020548 1 DBI 211070_x_at BC006466 1 DBI 201572_x_at NM_001921 1 DCTD 208619_at L40326 1 DDB1 212690_at AB018268 1 DDHD2 208674_x_at D29643 1 DDOST 203758_s_at NM_018380 1 DDX28 221699_s_at AF334103 1 DDX50 220482_s_at NM_012139 1 DELGEF 221509_at AB014731 1 DENR 206752_s_at NM_004402 1 DFFB 203816_at NM_001929 1 DGUOK 209549_s_at BC001121 1 DGUOK 202481_at NM_004735 DHRS3 202031_s_at NM_015610 1 DKFZP434J154 213701_at AW299245 1 DKFZp434N2030 222149_x_at AL137398 1 DKFZp434P162 212936_at AI927701 1 DKFZP564D172 208091_s_at NM_030796 1 DKFZP564K0822 221596_s_at AL136619 1 DKFZP564O0523 202537_s_at NM_014043 1 DKFZP564O123 210006_at BC002571 1 DKFZP564O243 213149_at AW299740 1 DLAT 205677_s_at NM_005887 1 DLEU1 208810_at AF080569 1 DNAJB6 212467_at AB014578 1 DNAJC13 213088_s_at BE551340 1 DNAJC9 213092_x_at AW241779 1 DNAJC9 217917_s_at NM_014183 1 DNCL2A 212538_at AL576253 1 DOCK9 221677_s_at AF232674 1 DONSON 219452_at NM_022355 1 DPEP2 219373_at NM_018973 1 DPM3 208370_s_at NM_004414 1 DSCR1 218576_s_at NM_007240 1 DUSP12 208956_x_at AB049113 1 DUT 209033_s_at D86550 1 DYRK1A 207232_s_at NM_014648 1 DZIP3 221586_s_at U15642 1 E2F5 220942_x_at NM_014367 1 E2IG5 219787_s_at NM_018098 1 ECT2 208883_at BF515424 1 EDD 209058_at AB002282 1 EDF1 209059_s_at AB002282 1 EDF1 212410_at AI346431 1 EFHA1 218438_s_at NM_025205 1 EG1 218696_at NM_004836 1 EIF2AK3 218287_s_at NM_012199 1 EIF2C1 212716_s_at AW083133 1 eIF3k 208756_at U36764 1 EIF3S2 201437_s_at NM_001968 1 EIF4E 214919_s_at R39094 1 EIF4EBP3, MASK-BP3 210839_s_at D45421 1 ENPP2 202596_at BC000436 1 ENSA 212681_at AI770004 1 EPB41L3 202909_at NM_014805 1 EPM2AIP1 202776_at NM_014597 1 ERBP 200043_at NM_004450 1 ERH 218100_s_at NM_018010 1 ESRRBL1 202942_at NM_001985 1 ETFB 205530_at NM_004453 1 ETFDH 217838_s_at NM_016337 1 EVL 215136_s_at AL050353 1 EXOSC8 32259_at AB002386 1 EZH1 202862_at NM_000137 1 FAH 218504_at NM_016044 1 FAHD2A 220643_s_at NM_018147 1 FAIM 209405_s_at BC002934 1 FAM3A 38043_at X55448 1 FAM3A 201889_at NM_014888 1 FAM3C 204283_at NM_006567 1 FARS1 211623_s_at M30448 1 FBL 222119_s_at AL117620 1 FBXO11 212231_at AB020682 1 FBXO21 218432_at NM_012175 1 FBXO3 206759_at NM_002002 1 FCER2 210889_s_at M31933 1 FCGR2B 203620_s_at NM_014824 1 FCHSD2 203115_at AU152635 1 FECH 201540_at NM_001449 1 FHL1 214505_s_at AF220153 1 FHL1 221007_s_at NM_030917 1 FIPIL1 219117_s_at NM_016594 1 FKBP11 219118_at NM_016594 1 FKBP11 218003_s_at M90820 1 FKBP3 218349_s_at AA824298 1 FLJ10036 205510_s_at NM_017976 1 FLJ10038 219648_at NM_018000 1 FLJ10116 218067_s_at NM_018011 1 FLJ10154 218974_at NM_018013 1 FLJ10159 218004_at NM_018045 1 FLJ10276 217900_at NM_018060 1 FLJ10326 221934_s_at BF941492 1 FLJ10496 218314_s_at AA024582 1 FLJ10726 217884_at NM_024662 1 FLJ10774 218125_s_at NM_018246 1 FLJ10853 203941_at NM_018250 1 FLJ10871 53720_at AI862559 1 FLJ11286 213064_at N64802 1 FLJ11806 218341_at NM_024664 1 FLJ11838 219022_at NM_022895 1 FLJ12448 217866_at NM_024811 1 FLJ12529 46142_at AI003763 1 FLJ12681 218179_s_at NM_021942 1 FLJ12716 220199_s_at NM_022831 1 FLJ12806 44065_at AI937468 1 FLJ14827 219798_s_at NM_019606 1 FLJ20257 209672_s_at AL136892 1 FLJ20323 206583_at NM_017776 1 FLJ20344 221222_s_at NM_017860 1 FLJ20519 219751_at NM_024860 1 FLJ21148 218531_at NM_025124 1 FLJ21749 218262_at NM_022762 1 FLJ22318 219176_at NM_024520 1 FLJ22555 219880_at NM_022907 1 FLJ23053 220169_at NM_024943 1 FLJ23235 64432_at W05463 1 FLJ39616 218053_at NM_017892 1 FNBP3 202304_at NM_014923 1 FNDC3 203064_s_at NM_004514 1 FOXK2 209702_at U79260 1 FTO 205324_s_at NM_012280 1 FTSJ1 218356_at NM_013393 1 FTSJ2 212847_at AL036840 1 FUBP1 214093_s_at AA156865 1 FUBP1 202231_at NM_006360 1 GA17 204618_s_at NM_005254 1 GABPB2 219815_at NM_024637 1 GAL3ST4 213049_at BG436400 1 GARNL1 214855_s_at AL050050 1 GARNL1 209729_at BC001782 1 GAS2L1 201738_at NM_005875 1 GC20 212139_at D86973 1 GCN1L1 208913_at AA868560 1 GGA2 200681_at NM_006708 1 GLO1 209883_at AF288389 1 GLT25D2 218913_s_at NM_016573 1 GMIP 214157_at AA401492 1 GNAS 202382_s_at NM_005471 1 GNPDA1 202106_at NM_005895 1 GOLGA3 201056_at N53479 1 GOLGB1 208843_s_at BC001408 1 GORASP2 209470_s_at D49958 1 GPM6A 204793_at NM_014710 1 GPRASP1 201106_at NM_002085 1 GPX4 204396_s_at NM_005308 1 GRK5 201520_s_at BF034561 1 GRSF1 215438_x_at BE906054 1 GSPT1 201912_s_at NM_002094 1 GSPT1 202680_at NM_002095 1 GTF2E2 213357_at AV701318 1 GTF2H5 201338_x_at NM_002097 1 GTF3A 215091_s_at BE542815 1 GTF3A 218343_s_at NM_012086 1 GTF3C3 200075_s_at BC006249 1 GUK1 220936_s_at NM_018267 1 H2AFJ 200853_at NM_002106 1 H2AFZ 200080_s_at AI955655 1 H3F3A 208630_at AI972144 1 HADHA 201036_s_at NM_005327 1 HADHSC 211569_s_at AF001903 1 HADHSC 202042_at NM_002109 1 HARS 203138_at NM_003642 1 HAT1 204018_x_at NM_000558 1 HBA1, HBA2 214414_x_at T50399 1 HBA2 209116_x_at M25079 1 HBB 211696_x_at AF349114 1 HBB 209274_s_at BC002675 1 HBLD2 202299_s_at NM_006402 1 HBXIP 202300_at NM_006402 1 HBXIP 215985_at X92110 1 HCG8 202957_at NM_005335 1 HCLS1 218620_s_at NM_016173 1 HEMK1 200093_s_at N32864 1 HINT1 218946_at NM_015700 1 HIRIP5 205671_s_at NM_002120 1 HLA-DOB 203290_at NM_002122 1 HLA-DQA1 200679_x_at NM_002128 1 HMGB1 208808_s_at BC000903 1 HMGB2 200943_at NM_004965 1 HMGN1 200944_s_at NM_004965 1 HMGN1 209787_s_at BC001282 1 HMGN4 209068_at D89678 1 HNRPDL 208990_s_at AI912352 1 HNRPH3 214918_at AK024911 1 HNRPM 208766_s_at BC001449 1 HNRPR 208713_at BF724216 1 HNRPUL1 203202_at AI950314 1 HRB2 203203_s_at NM_007043 1 HRB2 202098_s_at NM_001535 1 HRMT1L1 221564_at AL570294 1 HRMT1L1 206445_s_at NM_001536 1 HRMT1L2 209657_s_at M65217 1 HSF2 220839_at NM_014168 1 HSPC133 221570_s_at AF201938 1 HSPC133 217774_s_at NM_016404 1 HSPC152 218728_s_at AK024569 1 HSPC163 210211_s_at AF028832 1 HSPCA 205133_s_at NM_002157 1 HSPE1 202602_s_at NM_014500 1 HTATSF1 212493_s_at AI761110 1 HYPB 204744_s_at NM_013417 1 IARS 210970_s_at AF235049 1 IBTK 204868_at NM_001545 1 ICT1 202070_s_at NM_005530 1 IDH3A 222285_at AW134608 1 IGHD 209374_s_at BC001872 1 IGHM 212827_at X17115 1 IGHM 209341_s_at AU153366 1 IKBKB 204116_at NM_000206 1 IL2RG 221548_s_at AY024365 1 ILKAP 212411_at BE747342 1 IMP4 205981_s_at NM_001564 1 ING1L 48825_at AA887083 1 ING4 204552_at AA355179 1 INPP4A 204202_at NM_017604 1 IQCE 217908_s_at NM_018442 1 IQWD1 209075_s_at AY009128 1 ISCU 205055_at NM_002208 1 ITGAE 216178_x_at AA215854 1 ITGB1 202660_at AA834576 1 ITPR2 215791_at AF003738 1 ITSN1 212287_at BF382924 1 JJAZ1 210878_s_at BC001202 1 JMJD1B 214861_at AI341811 1 JMJD2C 200048_s_at NM_006694 1 JTB 218570_at NM_018095 1 KBTBD4 45653_at AW026481 1 KCTD13 218823_s_at NM_017634 1 KCTD9 212733_at AI798908 1 KIAA0226 212735_at AI798908 1 KIAA0226 212474_at D87682 1 KIAA0241 212450_at D87445 1 KIAA0256 209256_s_at AF277177 1 KIAA0265 212855_at D87466 1 KIAA0276 212621_at AB006624 1 KIAA0286 214356_s_at AI272899 1 KIAA0368 212480_at AB002374 1 KIAA0376 202713_s_at AA129755 1 KIAA0391 212068_s_at AB011087 1 KIAA0515 212485_at AU146596 1 KIAA0553 212675_s_at AB011154 1 KIAA0582 34406_at AB011174 1 KIAA0602 201965_s_at NM_015046 1 KIAA0625 212200_at AW274877 1 KIAA0692 212311_at AA522514 1 KIAA0746 209553_at BC001001 1 KIAA0804 212546_s_at AI126634 1 KIAA0826 204568_at NM_014924 1 KIAA0831 205594_at NM_014897 1 KIAA0924 209654_at BC004902 1 KIAA0947 203831_at NM_014925 1 KIAA1002 200861_at NM_016284 1 KIAA1007 55872_at AI493119 1 KIAA1196 221736_at BG236163 1 KIAA1219 219520_s_at NM_018458 1 KIAA1280 207314_x_at NM_006737 1 KIR3DL2 217906_at NM_014315 1 KLHDC2 208975_s_at BC003572 1 KPNB1 204009_s_at NM_004985 1 KRAS2 200914_x_at NM_004986 1 KTN1 200915_x_at NM_004986 1 KTN1, TXNDC7 214709_s_at Z22551 1 KTN1, TXNDC7 200771_at NM_002293 1 LAMC1 212137_at AV746402 1 LARP 34764_at D21851 1 LARS2 212446_s_at AI658534 1 LASS6 221515_s_at BC001214 1 LCMT1 202726_at NM_002314 1 LIG1 204357_s_at NM_002314 1 LIMK1 202386_s_at NM_019081 1 LKAP 213527_s_at AC002310 1 LOC146542 213703_at W95043 1 LOC150759 221973_at AI983904 1 LOC150759 214801_at W88821 1 LOC163590 211325_x_at U72518 1 LOC171220 212866_at AI081543 1 LOC203069 213725_x_at AI693140 1 LOC283824 219043_s_at NM_024065 1 LOC285359, PDCL3 221797_at AY007126 1 LOC339229 50374_at AA150503 1 LOC339229 222000_at AI915947 1 LOC339448 218303_x_at NM_016618 1 LOC51315 218616_at NM_020395 1 LOC57117 203897_at BE963444 1 LOC57149 213346_at BE748563 1 LOC93081 218096_at NM_018361 1 LPAAT-e 216250_s_at X77598 1 LPXN 221640_s_at AF274972 1 LRDD 211615_s_at M92439 1 LRPPRC 209449_at AF196468 1 LSM2 202737_s_at AA112507 1 LSM4 211747_s_at BC005938 1 LSM5 204559_s_at NM_016199 1 LSM7 212248_at AI886796 1 LYRIC 217536_x_at M78162 1 M78162 209014_at AF217963 1 MAGED1 220925_at NM_021929 1 MAK10 214703_s_at AW954107 1 MAN2B2 202670_at AI571419 1 MAP2K1 206854_s_at NM_003188 1 MAP3K7 202569_s_at NM_002376 1 MARK3 213671_s_at AA621558 1 MARS 212064_x_at AI471665 1 MAZ 209580_s_at AL556619 1 MBD4 201620_at NM_003791 1 MBTPS1 218440_at NM_020166 1 MCCC1 200978_at NM_005917 1 MDH1 209036_s_at BC001917 1 MDH2 212693_at BE670928 1 MDN1 218288_s_at NM_021825 1 MDS025 221706_s_at BC006005 1 MDS032 218061_at NM_014623 1 MEA 202645_s_at NM_000244 1 MEN1 207098_s_at NM_017927 1 MFN1 204153_s_at AI738965 1 MFNG 220189_s_at NM_014275 1 MGAT4B 219001_s_at NM_024345 1 MGC10765 213104_at AI799802 1 MGC24381 218903_s_at NM_024068 1 MGC2731 200076_s_at BC006479 1 MGC2749 218714_at NM_024031 1 MGC3121 209191_at BC002654 1 MGC4083 202365_at BC004815 1 MGC5139 221580_s_at BC001972 1 MGC5306 200847_s_at NM_016127 1 MGC8721 200899_s_at AK002091 1 MGEA5 217871_s_at BC000447 1 MIF 214246_x_at AI859060 1 MINK 221824_s_at AA770170 1 MIR 209845_at AF117233 1 MKRN1 204173_at NM_002475 1 MLC1SA 202520_s_at NM_000249 1 MLH1 204206_at NM_020310 1 MNT 212508_at AK024029 1 MOAP1 201994_at NM_012286 1 MORF4L2 215731_s_at X98258 1 MPHOSPH9 219162_s_at NM_016050 1 MRPL11 220526_s_at NM_017971 1 MRPL20 218339_at NM_014180 1 MRPL22 213897_s_at AI832239 1 MRPL23 209609_s_at BC004517 1 MRPL9 203800_s_at BG254653 1 MRPS14 221437_s_at NM_031280 1 MRPS15 212604_at AI937794 1 MRPS31 218654_s_at NM_016071 1 MRPS33 217942_at NM_021821 1 MRPS35 211783_s_at BC006177 1 MTA1 210212_x_at BC002600 1 MTCP1 216862_s_at Z24459 1 MTCP1 202309_at NM_005956 1 MTHFD1 216095_x_at AF057354 1 MTMR1 219822_at NM_004294 1 MTRF1 203199_s_at N29717 1 MTRR 205145_s_at NM_002477 1 MYL5 222018_at AI992187 1 NACA 204528_s_at NM_004537 1 NAP1L1 208753_s_at BC002387 1 NAP1L1 204749_at NM_004538 1 NAP1L3 218713_at NM_024611 1 NARG2 201517_at BC001255 1 NCBP2 218697_at NM_016453 1 NCKIPSD 200610_s_at NM_005381 1 NCL 217286_s_at BC001805 1 NDRG3 202298_at NM_004541 1 NDUFA1 209224_s_at BC003674 1 NDUFA2 217773_s_at NM_002489 1 NDUFA4 202785_at NM_005001 1 NDUFA7 208969_at AF050641 1 NDUFA9 202077_at NM_005003 1 NDUFAB1 218320_s_at NM_019056 1 NDUFB11 202839_s_at NM_004146 1 NDUFB7 203478_at NM_002494 1 NDUFC1 218101_s_at NM_004549 1 NDUFC2 201740_at NM_004551 1 NDUFS3 203189_s_at NM_002496 1 NDUFS8 203190_at NM_002496 1 NDUFS8 213331_s_at AV700007 1 NEK1 203413_at NM_006159 1 NELL2 218129_s_at BC005316 1 NFYB 202475_at NM_006326 1 NIFIE14 212483_at AB019494 1 NIPBL 203830_at NM_022344 1 NJMU-R1 202294_at NM_005862 1 NM_005862 217946_s_at NM_016402 1 NM_016402 219817_at NM_016534 1 NM_016534 218506_x_at NM_018459 1 NM_018459 218517_at NM_024900 1 NM_024900 212739_s_at AL523860 1 NME4 200875_s_at NM_006392 1 NOL5A 202882_x_at NM_016167 1 NOL7 204791_at NM_003297 1 NR2C1 204651_at AW003022 1 NRF1 213061_s_at AA643304 1 NTAN1 213062_at AA643304 1 NTAN1 212605_s_at AK025759 1 NUDT3 212182_at AB007956 1 NUDT4 202900_s_at NM_002532 1 NUP88 213018_at AI337901 1 ODAG 203569_s_at NM_003611 1 OFD1 219073_s_at NM_017784 1 OSBPL10 208717_at BC001669 1 OXA1L 206637_at NM_014879 1 P2RY14 218131_s_at AK024670 1 p66alpha 201545_s_at NM_004643 1 PABPN1 200816_s_at NM_000430 1 PAFAH1B1 208051_s_at NM_006451 1 PAIP1 209064_x_at BF248165 1 PAIP1 210466_s_at BC002488 1 PAI-RBP1 202759_s_at BE879367 1 PALM2-AKAP2 204715_at NM_015368 1 PANX1 212718_at BF797555 1 PAPOLA 200006_at NM_007262 1 PARK7 203905_at NM_002582 1 PARN 219033_at NM_024615 1 PARP8 213534_s_at D50925 1 PASK 204004_at AI336206 1 PAWR 205353_s_at NM_002567 1 PBP 210825_s_at AF130103 1 PBP 211941_s_at BE969671 1 PBP 214177_s_at AI935162 1 PBXIP1 212694_s_at NM_000532 1 PCCB 219737_s_at NM_020403 1 PCDH9 203378_at AB020631 1 PCF11 218260_at NM_024050 1 PCIA1 202174_s_at NM_006197 1 PCM1 218014_at NM_024844 1 PCNT1 205559_s_at NM_006200 1 PCSK5 212422_at AL547263 1 PDCD11 204025_s_at NM_002598 1 PDCD2 213581_at BF446180 1 PDCD2 203415_at NM_013232 1 PDCD6 204491_at R40917 1 PDE4D 214129_at AI821791 1 PDE4DIP 219575_s_at NM_022341 1 PDF, COG8 221811_at BF033007 1 PERLD1 219180_s_at AI817074 1 PEX26 205361_s_at AI718295 1 PFDN4 210908_s_at AB055804 1 PFDN5 204604_at NM_012395 1 PFTK1 222125_s_at BC000580 1 PH-4 212542_s_at BF224151 1 PHIP 202738_s_at BG149218 1 PHKB 202739_s_at NM_000293 1 PHKB 203335_at NM_006214 1 PHYH 209625_at BC004100 1 PIGH 209998_at BC001030 1 PIGO 202927_at NM_006221 1 PIN1 205632_s_at NM_003558 1 PIP5K1B 213111_at AB023198 1 PIP5K3 218667_at NM_022368 1 PJA1 54051_at H59033 1 PKNOX1 205372_at NM_002655 1 PLAG1 213309_at AL117515 1 PLCL2 219024_at NM_021622 1 PLEKHA1 201682_at NM_004279 1 PMPCB 213677_s_at BG434893 1 PMS1 218961_s_at NM_007254 1 PNKP 205901_at NM_006228 1 PNOC 209740_s_at U03886 1 PNPLA4 201115_at NM_006230 1 POLD2 217806_s_at NM_015584 1 POLDIP2 203366_at NM_002693 1 POLG 212955_s_at AL037557 1 POLR2I 218016_s_at NM_018119 1 POLR3E 203782_s_at NM_005035 1 POLRMT 213360_s_at AA514622 1 POM121, LOC340318 204839_at NM_015918 1 POP5 209482_at BC001430 1 POP7 205267_at NM_006235 1 POU2AF1 205661_s_at NM_025207 1 PP591 202494_at NM_006112 1 PP1E 212750_at AB020630 1 PPP1R16B 41577_at AB020630 1 PPP1R16B 202165_at BF966540 1 PPP1R2 207830_s_at NM_002713 1 PPP1R8 221772_s_at AI459157 1 PPP2R2D 201877_s_at NM_002719 1 PPP2R5C 202432_at NM_021132 1 PPP3CB 202741_at AA130247 1 PRKACB 207957_s_at NM_002738 1 PRKCB1 209685_s_at M13975 1 PRKCB1 208694_at U47077 1 PRKDC 220553_s_at NM_018333 1 PRPF39 209161_at AI184802 1 PRPF4 202127_at AB011108 1 PRPF4B 209440_at BC001605 1 PRPS1 203401_at NM_002765 1 PRPS2 202529_at NM_002766 1 PRPSAP1 203089_s_at NM_013247 1 PRSS25 209337_at AF063020 1 PSIP1 202244_at NM_002796 1 PSMB4 209503_s_at AF035309 1 PSMC5 212296_at NM_005805 1 PSMD14 200830_at NM_002808 1 PSMD2 212219_at D38521 1 PSME4 218371_s_at AA969958 1 PSPC1 219293_s_at NM_013341 1 PTD004 201433_s_at NM_014754 1 PTDSS1 213795_s_at AL121905 1 PTPRA 201166_s_at NM_014676 1 PUM1 216221_s_at D87078 1 PUM2 201608_s_at NM_007062 1 PWP1 201568_at NM_014402 1 QP-C 202754_at NM_015361 1 R3HDM 217763_s_at AF183421 1 RAB31 217764_s_at AF183421 1 RAB31 202373_s_at AF255648 1 RAB3-GAP150 218699_at NM_003929 1 RAB7L1 213313_at AI922519 1 RABGAP1 209181_s_at U49245 1 RABGGTB 219151_s_at NM_007081 1 RABL2A, RABL2B 207405_s_at NM_002873 1 RAD17 204199_at NM_014636 1 RALGPS1 220338_at NM_018037 1 RALGPS2 221809_at AB040897 1 RANBP10 211954_s_at BC000947 1 RANBP5 202582_s_at AF306510 1 RANBP9 218526_s_at NM_014185 1 RANGNRF 209444_at BC001851 1 RAP1GDS1 205169_at NM_005057 1 RBBP5 212781_at AK026954 1 RBBP6 201092_at NM_002893 1 RBBP7 57540_at AI823980 1 RBKS 204178_s_at NM_006328 1 RBM14 218117_at NM_014248 1 RBX1 201486_at NM_002902 1 RCN2 203898_at AU154853 1 RCP9 222203_s_at AK023625 1 RDH14 221532_s_at AF309553 1 REC14 210568_s_at BC001052 1 RECQL 219041_s_at NM_014374 1 REPIN1 202296_s_at NM_007033 1 RER1 218428_s_at NM_016316 1 REV1L 208070_s_at NM_002912 1 REV3L 203659_s_at NM_005798 1 RFP2 202976_s_at NM_014899 1 RHOBTB3 202130_at NM_003831 1 RIOK3 214663_at AB007941 1 RIPK5 213397_x_at AI761728 1 RNASE4 218496_at BG534527 1 RNASEH1 202683_s_at NM_003799 1 RNMT 200087_s_at AK024976 1 RNP24 212430_at AL109955 1 RNPC1 218462_at NM_025065 1 RPF1 222229_x_at AL121871 1 RPL26 218830_at NM_016093 1 RPL26L1 221593_s_at BC001663 1 RPL31 213687_s_at BE968801 1 RPL35A 210034_s_at AA582460 1 RPL5 211542_x_at BC004334 1 RPS10 200095_x_at AA320764 1 RPS10 213890_x_at AI200589 1 RPS16 200949_x_at NM_001023 1 RPS20 200091_s_at AA888388 1 RPS25 200741_s_at NM_001030 1 RPS27 200017_at NM_002954 1 RPS27A 218007_s_at BC003667 1 RPS27L 208904_s_at BF431363 1 RPS28 204635_at NM_004755 1 RPS6KA5 205540_s_at NM_016656 1 RRAGB 218088_s_at AK023373 1 RRAGC 208456_s_at NM_012250 1 RRAS2 203704_s_at AW118862 1 RREB1 201975_at NM_002956 1 RSN 212319_at AB007857 1 RUTBC1 201459_at NM_006666 1 RUVBL2 219598_s_at NM_016104 1 RWDD1 205087_at NM_015485 1 RWDD3 212438_at BG252325 1 RY1 213262_at AI932370 1 SACS 203280_at NM_014649 1 SAFB2 209486_at BC004546 1 SAS10 218276_s_at AI679398 1 SAV1 213244_at AI207792 1 SCAMP4 205790_at NM_003726 1 SCAP1 212140_at AB014548 1 SCC-112 202541_at BF589679 1 SCYE1 218607_s_at NM_018115 1 SDAD1 218649_x_at NM_004713 1 SDCCAG1 218427_at NM_006643 1 SDCCAG3 200945_s_at NM_014933 1 SEC31L1 219349_s_at NM_018303 1 SEC5L1 201916_s_at NM_007214 1 SEC63 212630_at AF055006 1 SEC6L1 218265_at NM_024077 1 SECISBP2 219351_at NM_014563 1 SEDL 221931_s_at AV701173 1 SEH1L 204563_at NM_000655 1 SELL 201194_at NM_003009 1 SEPW1 209723_at BC002538 1 SERPINB9 205352_at NM_005025 1 SERPINI1 205933_at NM_015559 1 SETBP1 216457_s_at AK026080 1 SF3A1 203818_s_at NM_006802 1 SF3A3 200685_at AU146237 1 SFRS11 200686_s_at NM_004768 1 SFRS11 214853_s_at AI091079 1 SHC1 205063_at NM_003616 1 SIP1 213600_at AA425633 1 SIPA1L3 219185_at NM_012241 1 SIRT5 203489_at NM_006427 1 SIVA 200718_s_at AA927664 1 SKP1A 207974_s_at NM_006930 1 SKP1A 205234_at NM_004696 1 SLC16A4 203775_at NM_014251 1 SLC25A13 218989_x_at NM_022902 1 SLC30A5 213082_s_at AJ005866 1 SLC35D2 218928_s_at NM_018964 1 SLC37A1 202111_at NM_003040 1 SLC4A2 209884_s_at AF047033 1 SLC4A7 215043_s_at X83301 1 SMA3, SMA5 201784_s_at NM_014267 1 SMAP 206544_x_at NM_003070 1 SMARCA2 218452_at NM_014140 1 SMARCAL1 201827_at AF113019 1 SMARCD2 218781_at NM_024624 1 SMC6L1 205596_s_at AY014180 1 SMURF2 202690_s_at BC001721 1 SNRPD1 203832_at NM_003095 1 SNRPF 212777_at L13857 1 SOS1 221239_s_at NM_030764 1 SPAP1 217927_at NM_014041 1 SPC12 212526_at AK002207 1 SPG20 205861_at NM_003121 1 SPIB 211704_s_at AF356353 1 SPIN2 212071_s_at BE968833 1 SPTBN1 218407_x_at NM_013349 1 SPUF 209218_at AF098865 1 SQLE 210959_s_at AF113128 1 SRD5A1 201247_at BE513151 1 SREBF2 205335_s_at NM_003135 1 SRP19 201273_s_at NM_003133 1 SRP9 202200_s_at NM_003137 1 SRPK1 218140_x_at NM_021203 1 SRPRB 201138_s_at NM_003142 1 SSB 201139_s_at NM_003142 1 SSB 202591_s_at NM_003143 1 SSBP1 208666_s_at BE866412 1 ST13 208667_s_at U17714 1 ST13 209023_s_at BC001765 1 STAG2 212549_at BE645861 1 STAT5B 211505_s_at AL136601 1 STAU 208855_s_at AF083420 1 STK24 217934_x_at NM_005861 1 STUB1 203310_at NM_007269 1 STXBP3 221213_s_at NM_017661 1 SUHW4 202829_s_at NM_005638 1 SYBL1 219156_at NM_018373 1 SYNJ2BP 200055_at NM_006284 1 TAF10 206613_s_at NM_005681 1 TAF1A 221508_at BC002756 1 TAOK3 201263_at NM_003191 1 TARS 209154_at AF234997 1 TAX1BP3 218466_at NM_024682 1 TBC1D17 203667_at NM_004607 1 TBCA 203715_at NM_003193 1 TBCE 213400_s_at AV753028 1 TBL1X 209820_s_at BC002361 1 TBL3 216241_s_at X57198 1 TCEA1 202371_at NM_024863 1 TCEAL4 209153_s_at M31523 1 TCF3 222146_s_at AK026674 1 TCF4 222010_at BF224073 1 TCP1 222011_s_at BF224073 1 TCP1 203054_s_at NM_022171 1 TCTA 203448_s_at AI347136 1 TERF1 212330_at R60866 1 TFDP1 218996_at NM_013342 1 TFPT 214977_at AK023852 1 TG 212910_at W19873 1 THAP11 213043_s_at AI023317 1 THRAP4 43544_at AA314406 1 THRAP5 218188_s_at NM_012458 1 TIMM13 203222_s_at NM_005077 1 TLE1 211077_s_at Z25421 1 TLK1 212997_s_at AU151689 1 TLK2 208942_s_at U93239 1 TLOC1 217979_at NM_014399 1 TM4SF13 208184_s_at NM_003274 1 TMEM1 209412_at U61500 1 TMEM1 218477_at NM_014051 1 TMEM14A 221452_s_at NM_030969 1 TMEM14B 202857_at NM_014255 1 TMEM4 209796_s_at BC001027 1 TMEM4 215346_at BF664114 1 TNFRSF5 206150_at NM_001242 1 TNFRSF7 48531_at AA522816 1 TNIP2 202561_at AF070613 1 TNKS 210886_x_at AB007457 1 TP53AP1 220865_s_at NM_014317 1 TPRT 213334_x_at BE676218 1 TREX2 210846_x_at AF220130 1 TRIM14 212544_at AI131008 1 TRIP3 202642_s_at NM_003496 1 TRRAP 215735_s_at AC005600 1 TSC2 214606_at BF129969 1 TSPAN-2 212928_at AL050331 1 TSPYL4 217968_at NM_003310 1 TSSC1 36936_at U58766 1 TSTA3 201434_at NM_003314 1 TTC1 217964_at NM_017775 1 TTC19 210645_s_at D83077 1 TTC3 213174_at BE675549 1 TTC9 202266_at NM_016614 1 TTRAP 209077_at AL022313 1 TXN2 201010_s_at NM_006472 1 TXNIP 37577_at U79256 1 U79256 202151_s_at NM_016172 1 UBADC1 209115_at AL117566 1 UBE1C 201343_at BE621259 1 UBE2D2 201344_at BF196642 1 UBE2D2 210024_s_at AB017644 1 UBE2E3 201002_s_at NM_003349 1 UBE2V1, Kua- UEV 218082_s_at NM_014517 1 UBP1 205687_at NM_019116 1 UBPH 212008_at N29889 1 UBXD2 218533_s_at NM_017859 1 UCKL1 209103_s_at BC001049 1 UFD1L 212074_at BE972774 1 UNC84A 206958_s_at AF318575 1 UPF3A 206959_s_at AF318575 1 UPF3A 214323_s_at N36842 1 UPF3A 202090_s_at NM_006830 1 UQCR 208909_at BC000649 1 UQCRFS1 208970_s_at M14016 1 UROD 203031_s_at NM_000375 1 UROS 200083_at AA621731 1 USP22 212388_at AB028980 1 USP24 220079_s_at NM_018391 1 USP48 2031171_s_at NM_014871 1 USP52 202745_at NM_005154 1 USP8 221514_at BC001149 1 UTP14A 218495_at NM_004182 1 UXT 207100_s_at NM_016830 1 VAMP1 214792_x_at AI955119 1 VAMP2 202550_s_at AF160212 1 VAPB 212038_s_at AL515918 1 VDAC1 203683_s_at NM_003377 1 VEGFB 208623_s_at J05021 1 VIL2 209950_s_at BC004300 1 VILL 205844_at NM_004666 1 VNN1 204376_at NM_014703 1 VprBP 220068_at NM_013378 1 VPREB3 212326_at AB007922 1 VPS13D 218022_at NM_016440 1 VRK3 221998_s_at BF062886 1 VRK3 213048_s_at W26593 1 W26593 213598_at W87688 1 W87688 221725_at AI962978 1 WASF2 200609_s_at NM_017491 1 WDR1 209216_at BC000464 1 WDR45 212533_at X62048 1 WEE1 203112_s_at NM_005663 1 WHSC2 34225_at AF101434 1 WHSC2 205672_at NM_000380 1 XPA 212160_at AI984005 1 XPOT 213077_at AL049305 1 YTHDC2 219186_at NM_020224 1 ZBTB7 217594_at R25849 1 ZCCHC11 212655_at AB011151 1 ZCCHC14 212860_at BG168720 1 ZDHHC18 220261_s_at NM_018106 1 ZDHHC4 220206_at NM_024772 1 ZMYM1 207605_x_at NM_024498 1 ZNF117 37254_at U09366 1 ZNF133 209565_at BC000832 1 ZNF183 202778_s_at NM_003453 1 ZNF198 214823_at AF033199 1 ZNF204 219925_at NM_007167 1 ZNF258 211009_s_at AF159567 1 ZNF271 216399_s_at AK025663 1 ZNF291 211678_s_at AF090934 1 ZNF313 209538_at U69645 1 ZNF32 218079_s_at NM_024835 1 ZNF403 221626_at AL136548 1 ZNF506 204291_at NM_014803 1 ZNF518 221645_s_at M27877 1 ZNF83 Table 2: Genetic markers which are differentially expressed between probable multiple sclerosis which further converted to the diagnosis of definite MS during a two-years follow up and healthy controls are provided (the Probeset ID of the Affymetrix Gene Chip), along with the corresponding GenBank accession number (GenBank Acc. No.), the gene symbol and the direction of change in gene expression (“1”- upregulation; “−1” - downregulation). Note that the p values of the TNOM, Info and t-Test statistical tests all passed the 95% confidence level.

Sustained probable MS: Analysis of the signature of non-convertors—Analyzing of probable MS patients that did not convert to definite MS during the 2-year follow-up period as compared to healthy controls identified a specific gene expression signature of 503 most informative genes that is characteristic to these patients (Table 3, hereinbelow).

TABLE 3 Differentially expressed markers between probable multiple sclerosis subjects which did not convert to the diagnosis of definite multiple sclerosis (non-convertors) and healthy controls GenBank Gene Probeset Acc. No. Dir Symbol 212126_at −1 BG391282 213002_at AA770596 −1 AA770596 207593_at NM_022169 −1 ABCG4 219935_at NM_007038 −1 ADAMTS5 216678_at AK000773 −1 AK000773 222252_x_at AK023354 −1 AK023354 216746_at AK024606 −1 AK024606 216774_at AK025325 −1 AK025325 216336_x_at AL031602 −1 AL031602 216822_x_at AL359763 −1 AL359763 216813_at AL512728 −1 AL512728 202920_at NM_001148 −1 ANK2 215764_x_at AA877641 −1 AP2A2 201168_x_at NM_004309 −1 ARHGDIA 213138_at M62324 −1 ARID5A 202208_s_at BC001051 −1 ARL7 219996_at NM_024708 −1 ASB7 215987_at AV654984 −1 AV654984 222303_at AV700891 −1 AV700891 222348_at AW971134 −1 AW971134 222329_x_at AW974816 −1 AW974816 205681_at NM_004049 −1 BCL2A1 213281_at BE327172 −1 BE327172 217921_at BE543064 −1 BE543064 215775_at BF084105 −1 BF084105 217591_at BF725121 −1 BF725121 201235_s_at BG339064 −1 BTG2 220509_at NM_018605 −1 C13orf10 201309_x_at NM_004772 −1 C5orf13 220614_s_at NM_024694 −1 C6orf103 205476_at NM_004591 −1 CCL20 205114_s_at NM_002983 −1 CCL3, CCL3L1, MGC12815 201884_at NM_004363 −1 CEACAM5 218177_at NM_020412 −1 CHMP1.5 216016_at AK027194 −1 CIAS1 216015_s_at AK027194 −1 CIAS1 206207_at NM_001828 −1 CLC 213622_at AI733465 −1 COL9A2 213504_at W63732 −1 COPS6 204533_at NM_001565 −1 CXCL10 203666_at NM_000609 −1 CXCL12 209774_x_at M57731 −1 CXCL2 207850_at NM_002090 −1 CXCL3 214421_x_at AV652420 −1 CYP2C9 218013_x_at NM_016221 −1 DCTN4 221780_s_at AF336851 −1 DDX27 220004_at NM_018665 −1 DDX43 221293_s_at NM_022047 −1 DEF6 213632_at M94065 −1 DHODH 33768_at L19267 −1 DMWD 215151_at AB014594 −1 DOCK10 201044_x_at AA530892 −1 DUSP1 201041_s_at NM_004417 −1 DUSP1 204794_at NM_004418 −1 DUSP2 213477_x_at AL515273 −1 EEF1A1 201694_s_at NM_001964 −1 EGR1 201693_s_at NM_001964 −1 EGR1 200596_s_at BE614908 −1 EIF3S10 204513_s_at NM_014800 −1 ELMO1 210651_s_at L41939 −1 EPHB2 205767_at NM_001432 −1 EREG 212106_at AB020694 −1 ETEA 201329_s_at NM_005239 −1 ETS2 211307_s_at U43677 −1 FCAR 218814_s_at NM_018252 −1 FLJ10874 220215_at NM_024804 −1 FLJ12606 219397_at NM_025147 −1 FLJ13448 218810_at NM_025079 −1 FLJ23231 58367_s_at AA429615 −1 FLJ23233 219617_at NM_024766 −1 FLJ23451 206548_at NM_024880 −1 FLJ23556 210414_at AF169675 −1 FLRT1 210933_s_at BC004908 −1 FSCN1 217370_x_at S75762 −1 FUS 209416_s_at AF083810 −1 FZR1 215308_at AF052148 −1 G22P1 209305_s_at AF078077 −1 GADD45B 219954_s_at NM_020973 −1 GBA3 207034_s_at NM_030379 −1 GLI2 205220_at NM_006018 −1 GPR109B 208524_at NM_005290 −1 GPR15 209945_s_at BC000251 −1 GSK3B 212291_at AI393355 −1 HIPK1 208026_at NM_003540 −1 HIST1H4F 208729_x_at D83043 −1 HLA-B 208812_x_at BC004489 −1 HLA-C, HLA-B 222126_at AI247494 −1 HRBL, IRS3L 206708_at NM_002158 −1 HTLF 36564_at W27419 −1 IBRDC3 202637_s_at AI608725 −1 ICAM1 215485_s_at AA284705 −1 ICAM1 202638_s_at NM_000201 −1 ICAM1 202438_x_at BF346014 −1 IDS 202081_at NM_004907 −1 IER2 201631_s_at NM_003897 −1 IER3 207901_at NM_002187 −1 IL12B 210118_s_at M15329 −1 IL1A 205067_at NM_000576 −1 IL1B 39402_at M15330 −1 IL1B 212657_s_at AW083357 −1 IL1RN 211506_s_at AF043337 −1 IL8 202859_x_at NM_000584 −1 IL8 208364_at NM_001566 −1 INPP4A 213146_at AA521267 −1 JMJD3 41386_i_at AB002344 −1 JMJD3 41387_r_at AB002344 −1 JMJD3 201465_s_at BC002646 −1 JUN 203751_x_at NM_005354 −1 JUND 207141_s_at U39196 −1 KCNJ3 212057_at AA206161 −1 KIAA0182 215137_at H92070 −1 KIAA0508 204403_x_at NM_014719 −1 KIAA0738 206966_s_at NM_016285 −1 KLF12 208467_at NM_007249 −1 KLF12 204012_s_at AL529189 −1 LCMT2 202068_s_at NM_000527 −1 LDLR 215462_at AI978990 −1 LOC149478 216084_at AL080137 −1 LOC389715 64899_at AA209463 −1 LPPR2 205193_at NM_012323 −1 MAFF 219442_at NM_024048 −1 MGC3020 209231_s_at BC004191 −1 MGC3248 207984_s_at NM_005374 −1 MPP2 210254_at L35848 −1 MS4A3 202247_s_at NM_004689 −1 MTA1 212452_x_at AF113514 −1 MYST4 205669_at NM_004540 −1 NCAM2 200855_at AW771910 −1 NCOR1 204888_s_at AF029729 −1 NEURL 207535_s_at NM_002502 −1 NFKB2 201502_s_at NM_020529 −1 NFKBIA 203927_at NM_004556 −1 NFKBIE 215720_s_at AL031778 −1 NFYA 220856_x_at NM_014128 −1 NM_014128 207783_x_at NM_017627 −1 NM_017627 208120_x_at NM_031221 −1 NM_031221 202340_x_at NM_002135 −1 NR4A1 210226_at D85245 −1 NR4A1 211973_at AW341200 −1 NUDT3 204435_at NM_014778 −1 NUPL1 208274_at NM_022375 −1 OCLM 213131_at R38389 −1 OLFM1 221344_at NM_013936 −1 OR12D2 214637_at BG437034 −1 OSM 205432_at NM_002557 −1 OVGP1 206880_at NM_005446 −1 P2RXL1 215823_x_at U64661 −1 PABPC1, PABPC3 204267_x_at NM_004203 −1 PKMYT1 207717_s_at NM_004572 −1 PKP2 204691_x_at NM_003560 −1 PLA2G6 202924_s_at AF006005 −1 PLAGL2 205934_at NM_006226 −1 PLCL1 203471_s_at NM_002664 −1 PLEK 201489_at BC005020 −1 PPIF 37028_at U83981 −1 PPP1R15A 202014_at NM_014330 −1 PPP1R15A 205643_s_at NM_004576 −1 PPP2R2B 203317_at NM_012455 −1 PSD4 204748_at NM_000963 −1 PTGS2 206157_at NM_002852 −1 PTX3 34478_at X79780 −1 RAB11B 205461_at NM_006861 −1 RAB35 204543_at NM_005312 −1 RAPGEF1 203750_s_at NM_000964 −1 RARA 209936_at AF107493 −1 RBM5 216153_x_at AK022897 −1 RECK 209637_s_at AF030111 −1 RGS12 221989_at AW057781 −1 RPL10 215620_at AU147182 −1 RREB1 205485_at NM_000540 −1 RYR1 215670_s_at AK022844 −1 SCAND2 217331_at U63542 −1 SCC-112 208124_s_at NM_004263 −1 SEMA4F 213742_at AW241752 −1 SFRS11 222169_x_at N71739 −1 SH2D3A 214623_at AA845710 −1 SHFM3P1 220000_at NM_003830 −1 SIGLEC5 210796_x_at D86359 −1 SIGLEC6 203125_x_at AF046997 −1 SLC11A2 208389_s_at NM_004171 −1 SLC1A2 220091_at NM_017585 −1 SLC2A6 210001_s_at AB005043 −1 SOCS1 203372_s_at NM_003877 −1 SOCS2 215223_s_at W46388 −1 SOD2 215078_at AL050388 −1 SOD2 217576_x_at BF692958 −1 SOS2 210693_at BC001788 −1 SPPL2B 202021_x_at AF083441 −1 SUI1 207684_at NM_004608 −1 TBX6 221473_x_at U49188 −1 TDE1 211769_x_at BC006088 −1 TDE1 201109_s_at AV726673 −1 THBS1 201110_s_at NM_003246 −1 THBS1 214657_s_at AU134977 −1 TncRNA 207113_s_at NM_000594 −1 TNF 202643_s_at AI738896 −1 TNFAIP3 202644_s_at NM_006290 −1 TNFAIP3 206025_s_at AW188198 −1 TNFAIP6 216042_at AI275938 −1 TNFRSF25 212260_at AL045800 −1 TNRC15 204080_at NM_025077 −1 TOE1 212869_x_at AI721229 −1 TPT1 211943_x_at AL565449 −1 TPT1 214327_x_at AI888178 −1 TPT1 212284_x_at BG498776 −1 TPT1 220205_at NM_013315 −1 TPTE 213593_s_at AW978896 −1 TRA2A 205558_at NM_004620 −1 TRAF6 213191_at AF070530 −1 TRIF 209013_x_at AF091395 −1 TRIO 207490_at NM_025019 −1 TUBA4 201378_s_at NM_014847 −1 UBAP2L 215577_at AU146791 −1 UBE2E1 211403_x_at AF167079 −1 VCX-C, VCX2, VCX3, VCY, VCX 214758_at AL080157 −1 WDR21 218851_s_at NM_018383 −1 WDR33 216036_x_at AK001734 −1 WDTC1 222180_at AU147889 −1 YES1 219312_s_at NM_023929 −1 ZBTB10 203602_s_at NM_003443 −1 ZBTB17 216350_s_at X52332 −1 ZNF10 219228_at NM_018555 −1 ZNF331 220836_at NM_017757 −1 ZNF407 220086_at NM_022466 −1 ZNFN1A5 43511_s_at AI201594 1 DKFZp762 M127 217480_x_at M20812 1 Ig kappa chain 212993_at AA114166 1 XP_316923.1 212583_at AB011132 1 AB011132 209307_at AB014540 1 AB014540 217239_x_at AF044592 1 AF044592 210183_x_at AF112222 1 AF112222 217939_s_at NM_017657 1 AFTIPHILIN 204057_at AI073984 1 AI073984 222273_at AI419423 1 AI419423 206513_at NM_004833 1 AIM2 214259_s_at AI144075 1 AKR7A2 209200_at AL536517 1 AL536517 218203_at NM_013338 1 ALG5 209425_at AA888589 1 AMACR 202204_s_at NM_001144 1 AMFR 218230_at AL044651 1 ARFIP1 201229_s_at BC000422 1 ARIH2 202564_x_at NM_001667 1 ARL2 203487_s_at NM_015396 1 ARMC8 214749_s_at AK000818 1 ARMCX6 213238_at AI478147 1 ATP10D 208898_at AF077614 1 ATP6V1D 212559_at AU148827 1 AU148827 219667_s_at NM_017935 1 BANK1 214836_x_at BG536224 1 BG536224 207655_s_at NM_013314 1 BLNK 220059_at NM_012108 1 BRDG1 207369_at Z97632 1 BRS3 213410_at AL050102 1 C10orf137 219012_s_at AK023651 1 C11orf30 220240_s_at NM_017905 1 C13orf11 216263_s_at AK022215 1 C14orf120 213508_at AA142942 1 C14orf147 221932_s_at AA133341 1 C14orf87 52285_f_at AW002970 1 C18orf9 219283_at NM_014158 1 C1GALT2 217737_x_at NM_016407 1 C20orf43 221196_x_at NM_024332 1 C6.1A 220329_s_at NM_017909 1 C6orf96 204480_s_at NM_024112 1 C9orf16 200622_x_at AV685208 1 CALM3 205034_at NM_004702 1 CCNE2 216379_x_at AK000168 1 CD24 200983_x_at BF983379 1 CD59 215925_s_at AF283777 1 CD72 202892_at NM_004661 1 CDC23 211804_s_at AB012305 1 CDK2 204661_at NM_001803 1 CDW52 219375_at NM_006090 1 CEPT1 213375_s_at N80918 1 CG018 218102_at NM_015954 1 CGI-26 33307_at AL022316 1 CGI-96 214426_x_at BF062223 1 CHAF1A 220496_at NM_016509 1 CLEC2 202799_at NM_006012 1 CLPP 222043_at AI982754 1 CLU 219301_s_at NM_014141 1 CNTNAP2 212189_s_at AK022874 1 COG4 218328_at NM_016035 1 COQ4 213735_s_at AI557312 1 COX5B 201597_at NM_001865 1 COX7A2 204920_at AF154830 1 CPS1 203633_at BF001714 1 CPT1A 203804_s_at NM_006107 1 CROP 203445_s_at NM_005730 1 CTDSP2 200932_s_at NM_006400 1 DCTN2 203785_s_at NM_018380 1 DDX28 209549_s_at BC001121 1 DGUOK 202532_s_at NM_000791 1 DHFR 220985_s_at NM_030954 1 DKFZP564A022 213647_at D42046 1 DNA2L 221689_s_at AB035745 1 DSCR5 204841_s_at NM_003566 1 EEA1 206254_at NM_001963 1 EGF 204410_at NM_004681 1 EIF1AY 202461_at NM_014239 1 EIF2B2 208985_s_at BC002719 1 EIF3S1 208688_x_at U78525 1 EIF3S9 204505_s_at NM_001978 1 EPB49 203249_at AB002386 1 EZH1 218504_at NM_016044 1 FAHD2A 222056_s_at AA723370 1 FAHD2A 201863_at NM_014077 1 FAM32A 38043_at X55448 1 FAM3A 220408_x_at NM_017569 1 FAM48A 209630_s_at U87460 1 FBXW2 210889_s_at M31933 1 FCGR2B 217518_at BF056029 1 FER1L3 210298_x_at AF098518 1 FHL1 201540_at NM_001449 1 FHL1 208255_s_at NM_012181 1 FKBP8 219130_at NM_019083 1 FLJ10287 218179_s_at NM_021942 1 FLJ12716 221777_at BE966197 1 FLJ14827 219802_at NM_024854 1 FLJ22028 220169_at NM_024943 1 FLJ23235 205140_at NM_003838 1 FPGT 204145_at NM_004477 1 FRG1 209729_at BC001782 1 GAS2L1 204220_at NM_004877 1 GMFG 204000_at NM_016194 1 GNB5 218361_at NM_018178 1 GPP34R 222155_s_at AK021918 1 GPR172A 201106_at NM_002085 1 GPX4 201501_s_at NM_002092 1 GRSF1 203577_at NM_001517 1 GTF2H4 218343_s_at NM_012086 1 GTF3C3 221942_s_at AI719730 1 GUCY1A3 203817_at W93728 1 GUCY1B3 213515_x_at AI133353 1 HBG2 209273_s_at BG387555 1 HBLD2 204689_at NM_001529 1 HHEX 215933_s_at Z21533 1 HHEX 220387_s_at NM_007071 1 HHLA3 218525_s_at NM_017902 1 HIF1AN 203932_at NM_002118 1 HLA-DMB 205671_s_at NM_002120 1 HLA-DOB 200904_at X56841 1 HLA-E 213793_s_at BE550452 1 HOMER1 203914_x_at NM_000860 1 HPGD 210112_at U96721 1 HPS1 217869_at NM_016142 1 HSD17B12 221791_s_at BG167522 1 HSPC016 221711_s_at BC006244 1 HSPC142 221622_s_at AF246240 1 HT007 207180_s_at NM_006410 1 HTAT1P2 209586_s_at AF123539 1 HTCD37 219209_at NM_022168 1 IFIH1 203595_s_at N47725 1 IFIT5 211868_x_at AJ225092 1 IGHG1 212592_at AV733266 1 IGJ 221651_x_at BC005332 1 IGKC 216207_x_at AW408194 1 IGKV1D-13 215121_x_at AA680302 1 IGLC2 48825_at AA887083 1 ING4 204202_at NM_017604 1 IQCE 206493_at NM_000419 1 ITGA2B 206494_s_at NM_000419 1 ITGA2B 211945_s_at BG500301 1 ITGB1 216261_at AI151479 1 ITGB3 213483_at AK025679 1 KIAA0073 202503_s_at NM_014736 1 KIAA0101 212149_at AW470003 1 KIAA0143 212523_s_at D63480 1 KIAA0146 212733_at AI798908 1 KIAA0226 204876_at NM_014699 1 KIAA0296 76897_s_at AA628140 1 KIAA0674 212548_s_at BF515124 1 KIAA0826 207314_x_at NM_006737 1 KIR3DL2 201553_s_at NM_005561 1 LAMP1 203042_at NM_002294 1 LAMP2 221515_s_at BC001214 1 LCMT1 221274_s_at NM_030805 1 LMAN2L 213408_s_at AK024034 1 LOC220686, PIK4CA 216250_s_at X77598 1 LPXN 35974_at U10485 1 LRMP 210044_s_at BC002796 1 LYL1 201384_s_at NM_005899 1 M17S2 218573_at NM_014061 1 MAGEH1 206854_s_at NM_003188 1 MAP3K7 222036_s_at AI859865 1 MCM4 209199_s_at L08895 1 MEF2C 202645_s_at NM_000244 1 MEN1 217043_s_at U95822 1 MFN1 217022_s_at S55735 1 MGC27165 201764_at NM_024056 1 MGC5576 214364_at W84525 1 MGC61716 213528_at AL035369 1 MGC9084 205612_at NM_007351 1 MMRN1 218853_s_at NM_019556 1 MOSPD1 218339_at NM_014180 1 MRPL22 203095_at NM_002453 1 MTIF2 210386_s_at BC001906 1 MTX1 203517_at NM_006554 1 MTX2 202960_s_at NM_000255 1 MUT 203359_s_at NM_012333 1 MYCBP 200027_at NM_004539 1 NARS 202607_at AL526632 1 NDST1 209224_s_at BC003674 1 NDUFA2 202839_s_at NM_004146 1 NDUFB7 218101_s_at NM_004549 1 NDUFC2 217896_s_at NM_024946 1 NIP30 213682_at AL036344 1 NUP50 213018_at AI337901 1 ODAG 205301_s_at NM_016820 1 OGG1 203351_s_at NM_002552 1 ORC4L 37966_at AA187563 1 PARVB 37965_at AA181053 1 PARVB 216253_s_at N73272 1 PARVB 213652_at AU152579 1 PCSK5 207414_s_at NM_002570 1 PCSK6 219180_s_at AI817074 1 PEX26 206390_x_at NM_002619 1 PF4 202739_s_at NM_000293 1 PHKB 217097_s_at AC004990 1 PHTF2 207081_s_at NM_002650 1 PIK4CA 202732_at NM_007066 1 PKIG 201410_at AI983043 1 PLEKHB2 212719_at AB011178 1 PLEKHE1 201682_at NM_004279 1 PMPCB 219317_at NM_007195 1 POLI 202306_at NM_002696 1 POLR2G 212955_s_at AL037557 1 POLR2I 209382_at U93867 1 POLR3C 209482_at BC001430 1 POP7 202884_s_at T79584 1 PPP2R1B 200844_s_at BE869583 1 PRDX6 201805_at NM_002733 1 PRKAG1 207808_s_at NM_000313 1 PROS1 202529_at NM_002766 1 PRPSAP1 201316_at AL523904 1 PSMA2 204279_at NM_002800 1 PSMB9 201068_s_at NM_002803 1 PSMC2 200830_at NM_002808 1 PSMD2 202009_at NM_007284 1 PTK9L 219178_at NM_024638 1 QTRTD1 220964_s_at NM_030981 1 RAB1B 217763_s_at AF183421 1 RAB31 217764_s_at AF183421 1 RAB31 214552_s_at AF098638 1 RABEP1 203020_at NM_014857 1 RABGAP1L 222077_s_at AU153848 1 RACGAP1 221809_at AB040897 1 RANBP10 202297_s_at AF157324 1 RER1 202296_s_at NM_007033 1 RER1 209882_at AF084462 1 RIT1 218301_at NM_018226 1 RNPEPL1 218583_s_at NM_020640 1 RP42 209773_s_at BC001886 1 RRM2 209486_at BC004546 1 SAS10 202084_s_at NM_003003 1 SEC14L1 200961_at NM_012248 1 SEPHS2 217756_x_at NM_005770 1 SERF2 205933_at NM_015559 1 SETBP1 204688_at NM_003919 1 SGCE 213355_at AI989567 1 SIAT10 56256_at AA150165 1 SIDT2 219185_at NM_012241 1 SIRT5 201575_at NM_012245 1 SKIIP 203775_at NM_014251 1 SLC25A13 203658_at BC001689 1 SLC25A20 215043_s_at X83301 1 SMA3, SMA5 207827_x_at NM_007308 1 SNCA 206272_at NM_006542 1 SPHAR 201273_s_at NM_003133 1 SRP9 202811_at NM_006463 1 STAMBP 200028_s_at NM_020151 1 STARD7 208855_s_at AF083420 1 STK24 212990_at AB020717 1 SYNJ1 201259_s_at AI768845 1 SYPL 221397_at NM_023921 1 TAS2R10 209152_s_at M31523 1 TCF3 219292_at NM_018105 1 THAP1 201447_at AL567227 1 TIA1 217979_at NM_014399 1 TM4SF13 221246_x_at NM_018274 1 TNS 209917_s_at BC002709 1 TP53AP1 218095_s_at BC003545 1 TPARL 220865_s_at NM_014317 1 TPRT 203512_at NM_014408 1 TRAPPC3 217958_at NM_016146 1 TRAPPC4 204341_at NM_006470 1 TRIM16 210705_s_at AF220028 1 TRIM5 209778_at AF007217 1 TRIP11 215735_s_at AC005600 1 TSC2 221253_s_at NM_030810 1 TXNDC5 201588_at NM_004786 1 TXNL1 218289_s_at NM_024818 1 UBE1DC1 203281_s_at NM_003335 1 UBE1L 218533_s_at NM_017859 1 UCKL1 203583_at NM_014044 1 UNC50 209268_at AF165513 1 VPS45A 209452_s_at AF035824 1 VT11B 220917_s_at NM_025132 1 WDR19 217784_at NM_006555 1 YKT6 220261_s_at NM_018106 1 ZDHHC4 202939_at NM_005857 1 ZMPSTE24 201541_s_at NM_006349 1 ZNHIT1 Table 3: Provided are genetic markers which are differentially expressed between subjects diagnosed with probable multiple sclerosis which did not convert to the diagnosis of definite MS (non-convertors) during a two-years follow up and healthy controls (the Probeset ID of the Affymetrix Gene Chip), along with the corresponding GenBank accession number (GenBank Acc. No.), the gene symbol and the direction (Dir) of change in gene expression (“1” - upregulation; “−1” - downregulation). Note that the p values of the TNOM, Info and t-Test statistical tests all passed the 95% confidence level.

Gene expression pattern of subjects with definite diagnosis of multiple sclerosis—Table 4, hereinbelow, depict 722 genetic markers which are differentially expressed between subjects with a definite diagnosis of multiple sclerosis (both from relapse and remitting phases; blood samples were taken after the diagnosis of definite MS was confirmed, i.e., at least after the second neurological attack) and healthy controls.

TABLE 4 Differentially expressed markers between subjects with the diagnosis of definite multiple sclerosis and healthy controls GenBank Accession TNOM Info t-Test No, PValue PValue PValue Dir Gene Symbol AI252582 5.31E−06 5.31E−06 2.46E−05 −1 ATP6V0E NM_017686 5.31E−06 5.31E−06 1.44E−05 −1 GDAP2 NM_006404 2.90E−05 4.28E−05 1.23E−05 −1 PROCR NM_003916 1.49E−04 1.49E−04 8.21E−04 −1 AP1S2 NM_015396 1.49E−04 1.49E−04 2.46E−03 −1 ARMC8 NM_007212 1.49E−04 3.72E−05 5.28E−05 −1 RNF2 AL138761 1.49E−04 1.49E−04 3.67E−03 −1 — NM_020474 2.70E−04 1.90E−04 2.85E−02 −1 GALNT1 N21138 2.70E−04 1.90E−04 2.98E−04 −1 RHOBTB3 NM_015904 1.82E−03 1.47E−03 7.88E−03 −1 EIF5B NM_003201 1.82E−03 1.47E−03 4.89E−03 −1 TFAM NM_005263 1.82E−03 1.79E−03 1.67E−02 −1 GFI1 NM_022335 1.82E−03 2.96E−03 1.64E−04 −1 — NM_001222 1.82E−03 1.79E−03 3.87E−03 −1 SRP72 BC002456 1.82E−03 2.96E−03 1.85E−04 −1 — AW268817 1.82E−03 1.47E−03 3.21E−02 −1 CDC5L AB044661 1.82E−03 3.63E−04 7.50E−05 −1 XAB1 AK024044 1.82E−03 1.47E−03 8.77E−04 −1 SSA2 D42055 1.82E−03 1.79E−03 2.32E−03 −1 NEDD4 BF680255 1.82E−03 9.10E−04 4.33E−03 −1 — AW238654 1.82E−03 1.47E−03 1.83E−03 −1 — AK024584 1.82E−03 1.47E−03 2.95E−02 −1 — L40992 1.82E−03 1.79E−03 2.40E−02 −1 RUNX2 NM_014159 1.82E−03 1.47E−03 2.75E−03 −1 HYPB AL137750 1.82E−03 1.47E−03 1.87E−02 −1 ETNK1 AL567227 2.01E−03 2.88E−03 3.52E−02 −1 TIA1 NM_014774 2.01E−03 2.88E−03 4.00E−02 −1 KIAA0494 AU146275 2.01E−03 1.69E−03 1.55E−02 −1 ZNF161 NM_002717 2.01E−03 1.69E−03 6.85E−03 −1 PPP2R2A NM_004301 2.01E−03 2.88E−03 1.52E−03 −1 ACTL6A BE622627 2.01E−03 1.69E−03 1.83E−02 −1 PIK3R3 NM_005977 2.01E−03 2.55E−04 7.91E−04 −1 RNF6 NM_003616 2.01E−03 2.88E−03 9.81E−03 −1 SIP1 NM_005531 2.01E−03 1.69E−03 7.12E−04 −1 IFI16 NM_005849 2.01E−03 2.88E−03 1.29E−03 −1 IGSF6 NM_006065 2.01E−03 5.47E−04 1.08E−03 −1 SIRPB1 NM_003452 2.01E−03 2.88E−03 1.16E−02 −1 ZNF189 NM_003539 2.01E−03 2.88E−03 2.71E−03 −1 HIST1H4D NM_006016 2.01E−03 1.69E−03 1.81E−03 −1 CD164 AI332962 2.01E−03 1.69E−03 2.36E−03 −1 — BC004421 2.01E−03 1.21E−03 1.18E−03 −1 ZNF330 AB037701 2.01E−03 2.88E−03 5.57E−03 −1 SIP1 AB000815 2.01E−03 2.88E−03 8.15E−04 −1 ARNTL BC006403 2.01E−03 1.21E−03 1.38E−04 −1 NCK1 AB037703 2.01E−03 2.88E−03 1.25E−02 −1 SIP1 U90142 2.01E−03 1.21E−03 3.63E−04 −1 BTN2A1 AF234262 2.01E−03 2.88E−03 1.75E−03 −1 MAP3K2 M60725 2.01E−03 2.55E−04 1.06E−04 −1 RPS6KB1 AI057093 2.01E−03 1.69E−03 1.21E−03 −1 RDX AL079292 2.01E−03 2.88E−03 1.92E−02 −1 — AB002347 2.01E−03 2.55E−04 2.15E−03 −1 C6orf133 AL033377 2.01E−03 2.88E−03 4.63E−02 −1 GPR126 AI811577 2.01E−03 1.69E−03 2.03E−03 −1 ZNF184 AI860341 2.01E−03 1.69E−03 1.06E−03 −1 ACAA1 AF052146 2.01E−03 2.88E−03 1.12E−03 −1 — AK025174 2.01E−03 2.88E−03 4.88E−03 −1 GSDML AL096729 2.01E−03 1.69E−03 2.80E−02 −1 GSTA1 AK026712 2.01E−03 2.88E−03 4.93E−03 −1 — AL049325 2.01E−03 2.88E−03 2.30E−02 −1 CCM1 BC005316 2.01E−03 2.88E−03 2.52E−02 −1 NFYB NM_016618 2.01E−03 5.47E−04 6.92E−03 −1 LOC51315 NM_017423 2.01E−03 2.55E−04 6.86E−04 −1 GALNT7 NM_018046 2.01E−03 2.88E−03 7.75E−03 −1 VG5Q NM_018489 2.01E−03 1.69E−03 3.98E−04 −1 ASH1L NM_018293 2.01E−03 1.69E−03 1.80E−03 −1 FLJ10997 NM_018398 2.01E−03 1.69E−03 8.61E−03 −1 CACNA2D3 NM_018042 2.01E−03 2.88E−03 1.97E−03 −1 FLJ10260 NM_022488 2.01E−03 2.88E−03 5.03E−03 −1 APG3L NM_030934 2.01E−03 1.69E−03 9.89E−03 −1 C1orf25 AU157915 2.01E−03 2.88E−03 8.04E−03 −1 YTHDF3 BG167522 2.01E−03 2.88E−03 2.61E−02 −1 HSPC016 W72694 2.01E−03 2.55E−04 1.72E−03 −1 FAM26B NM_002136 9.49E−03 8.40E−03 1.84E−02 −1 HNRPA1 NM_005520 9.49E−03 8.40E−03 4.11E−03 −1 HNRPH1 NM_020474 9.49E−03 1.37E−02 1.53E−02 −1 GALNT1 NM_004048 9.49E−03 3.33E−03 1.95E−02 −1 B2M NM_005415 9.49E−03 7.52E−03 2.69E−03 −1 SLC20A1 AW051311 9.49E−03 1.56E−02 1.20E−02 −1 KPNA1 AB020335 9.49E−03 7.52E−03 1.85E−02 −1 SEL1L NM_002023 9.49E−03 1.37E−02 6.51E−03 −1 FMOD NM_005103 9.49E−03 1.37E−02 1.21E−03 −1 FEZ1 NM_000609 9.49E−03 7.52E−03 4.73E−02 −1 CXCL12 NM_003759 9.49E−03 1.37E−02 2.07E−02 −1 SLC4A4 NM_005589 9.49E−03 1.56E−02 1.03E−02 −1 ALDH6A1 NM_005630 9.49E−03 1.56E−02 2.48E−02 −1 SLCO2A1 NM_001046 9.49E−03 1.37E−02 2.06E−03 −1 SLC12A2 NM_005388 9.49E−03 7.52E−03 2.40E−02 −1 PDCL NM_005261 9.49E−03 8.40E−03 7.52E−03 −1 GEM NM_014254 9.49E−03 1.56E−02 1.21E−02 −1 TMEM5 NM_016656 9.49E−03 8.40E−03 7.06E−04 −1 RRAGB NM_002147 9.49E−03 7.52E−03 1.86E−02 −1 HOXB5 NM_004758 9.49E−03 1.37E−02 8.74E−03 −1 BZRAP1 NM_002547 9.49E−03 1.56E−02 5.79E−03 −1 OPHN1 NM_007366 9.49E−03 1.37E−02 8.98E−03 −1 PLA2R1 NM_001340 9.49E−03 8.40E−03 3.60E−03 −1 CYLC2 NM_015623 9.49E−03 7.52E−03 1.05E−02 −1 DKFZP564D166 AF116710 9.49E−03 7.52E−03 1.10E−02 −1 RPS14 BC000914 9.49E−03 7.52E−03 2.46E−03 −1 SFRS3 U40763 9.49E−03 1.37E−02 7.34E−03 −1 PPIG AB023200 9.49E−03 1.56E−02 4.79E−03 −1 C22orf19 L07515 9.49E−03 3.33E−03 3.32E−04 −1 CBX5 AB056663 9.49E−03 7.52E−03 1.00E−02 −1 ITCH AW003989 9.49E−03 3.63E−04 4.13E−03 −1 C19orf2 AF130104 9.49E−03 7.52E−03 1.37E−02 −1 — BC002713 9.49E−03 7.52E−03 1.04E−02 −1 MXD4 AF229180 9.49E−03 3.33E−03 4.12E−04 −1 AASS BE737027 9.49E−03 7.52E−03 1.79E−03 −1 — AI972268 9.49E−03 7.52E−03 1.65E−02 −1 PSME4 AA148507 9.49E−03 2.52E−03 6.95E−04 −1 SLC7A1 BG111635 9.49E−03 1.56E−02 2.16E−02 −1 CAST AI022882 9.49E−03 1.37E−02 2.36E−03 −1 PAM L43577 9.49E−03 7.52E−03 1.52E−02 −1 CXorf40 BE312027 9.49E−03 8.40E−03 1.81E−03 −1 — AK022846 9.49E−03 8.40E−03 1.60E−02 −1 INPP5B BG260658 9.49E−03 7.52E−03 2.00E−02 −1 — AW007137 9.49E−03 3.63E−04 2.91E−03 −1 — AI970731 9.49E−03 1.37E−02 2.38E−02 −1 RPS7 H71805 9.49E−03 1.56E−02 2.40E−03 −1 — AV717561 9.49E−03 1.23E−02 1.55E−03 −1 — AI613383 9.49E−03 1.56E−02 4.68E−03 −1 EEF1D W87901 9.49E−03 1.37E−02 4.57E−03 −1 — AK022065 9.49E−03 8.40E−03 1.10E−03 −1 RAB5A AJ010395 9.49E−03 3.33E−03 1.27E−02 −1 DKC1 AF113008 9.49E−03 2.52E−03 1.04E−03 −1 — AL359578 9.49E−03 3.33E−03 1.21E−03 −1 — AL049997 9.49E−03 8.40E−03 4.08E−02 −1 — U80771 9.49E−03 1.56E−02 9.34E−03 −1 — AF041811 9.49E−03 1.56E−02 1.10E−02 −1 NTRK3 AW088547 9.49E−03 7.52E−03 3.59E−02 −1 — NM_006717 9.49E−03 8.40E−03 2.15E−03 −1 SPIN NM_018145 9.49E−03 1.56E−02 3.83E−03 −1 FLJ10579 AA824298 9.49E−03 7.52E−03 3.28E−03 −1 FLJ10036 NM_016649 9.49E−03 1.37E−02 2.29E−03 −1 C20orf6 NM_018320 9.49E−03 1.56E−02 1.44E−02 −1 RNF121 NM_003973 9.49E−03 8.40E−03 4.82E−03 −1 — NM_017571 9.49E−03 8.40E−03 3.67E−03 −1 KIAA1212 NM_022101 9.49E−03 1.37E−02 1.07E−02 −1 FLJ22965 NM_014155 9.49E−03 7.52E−03 2.76E−02 −1 HSPC063 NM_024312 9.49E−03 8.40E−03 1.51E−02 −1 MGC4170 NM_024966 9.49E−03 3.33E−03 1.18E−03 −1 SEMA6D NM_018655 9.49E−03 7.52E−03 1.39E−02 −1 LENEP AF077053 9.49E−03 2.52E−03 2.54E−03 −1 TAF9L BE972394 9.49E−03 1.56E−02 1.79E−03 −1 ZNF131 BF195165 9.49E−03 1.56E−02 8.62E−03 −1 — BF224259 1.74E−02 2.19E−02 2.51E−02 −1 SMNDC1 BG168896 1.74E−02 2.72E−02 1.16E−02 −1 FNTA NM_012248 1.74E−02 7.75E−03 2.21E−03 −1 SEPHS2 BF739979 1.74E−02 2.72E−02 1.64E−02 −1 FLJ16518 AF053641 1.74E−02 5.43E−03 2.99E−02 −1 CSE1L BC002513 1.74E−02 2.72E−02 1.15E−02 −1 EIF2S1 NM_001020 1.74E−02 5.43E−03 3.65E−02 −1 RPS16 NM_003589 1.74E−02 2.19E−02 2.94E−02 −1 CUL4A AL567227 1.74E−02 2.19E−02 1.49E−02 −1 TIA1 NM_022037 1.74E−02 5.43E−03 1.66E−03 −1 TIA1 NM_002806 1.74E−02 5.43E−03 4.98E−03 −1 PSMC6 D42063 1.74E−02 2.72E−02 1.35E−02 −1 RANBP2 AF185696 1.74E−02 2.19E−02 2.04E−02 −1 OSBP NM_001560 1.74E−02 2.19E−02 4.92E−02 −1 IL13RA1 AI984051 1.74E−02 5.47E−04 4.24E−05 −1 THRAP1 AA156948 1.74E−02 2.19E−02 7.17E−03 −1 PRPF4B NM_016553 1.74E−02 7.75E−03 2.86E−03 −1 NUP62 AF302110 1.74E−02 5.43E−03 7.85E−03 −1 AASDHPPT NM_003601 1.74E−02 2.19E−02 1.40E−02 −1 SMARCA5 NM_006178 1.74E−02 5.43E−03 4.00E−03 −1 NSF BC000365 1.74E−02 2.19E−02 8.40E−03 −1 GTF2H1 AA834576 1.74E−02 5.43E−03 1.05E−02 −1 ITPR2 NM_003903 1.74E−02 2.19E−02 9.52E−03 −1 CDC16 NM_006460 1.74E−02 5.43E−03 7.32E−03 −1 HIS1 NM_004661 1.74E−02 2.19E−02 4.09E−02 −1 CDC23 NM_003850 1.74E−02 5.43E−03 1.17E−02 −1 SUCLA2 NM_006421 1.74E−02 2.72E−02 4.86E−02 −1 ARFGEF1 NM_000255 1.74E−02 2.19E−02 1.71E−02 −1 MUT NM_005783 1.74E−02 5.43E−03 3.12E−02 −1 TXNDC9 NM_013450 1.74E−02 5.43E−03 1.03E−02 −1 BAZ2B NM_003194 1.74E−02 2.19E−02 3.67E−02 −1 TBP NM_014663 1.74E−02 2.72E−02 1.21E−02 −1 JMJD2A BG111661 1.74E−02 2.72E−02 4.74E−02 −1 GOLGA1 AU157008 1.74E−02 2.72E−02 5.92E−03 −1 PSMD5 NM_003674 1.74E−02 5.43E−03 3.21E−02 −1 CDK10 NM_025137 1.74E−02 5.43E−03 1.19E−02 −1 FLJ21439 NM_021645 1.74E−02 5.43E−03 3.23E−02 −1 UTP14C NM_001114 1.74E−02 5.43E−03 3.34E−03 −1 ADCY7 NM_005923 1.74E−02 1.18E−02 1.58E−03 −1 MAP3K5 NM_002118 1.74E−02 2.19E−02 3.48E−02 −1 HLA-DMB NM_007049 1.74E−02 2.72E−02 8.46E−03 −1 BTN2A1 NM_005999 1.74E−02 2.19E−02 4.44E−02 −1 TSNAX NM_006493 1.74E−02 2.19E−02 2.88E−02 −1 CLN5 U16307 1.74E−02 5.43E−03 2.50E−03 −1 HRB2 NM_004379 1.74E−02 2.19E−02 1.85E−03 −1 CREB1 NM_002048 1.74E−02 2.19E−02 2.16E−02 −1 GAS1 AB011092 1.74E−02 1.18E−02 1.68E−03 −1 ADCY9 NM_004898 1.74E−02 2.19E−02 9.45E−03 −1 CLOCK NM_003631 1.74E−02 2.43E−02 6.33E−03 −1 PARG NM_002643 1.74E−02 2.72E−02 4.22E−02 −1 PIGF NM_014950 1.74E−02 2.19E−02 9.23E−03 −1 ZBTB1 NM_003838 1.74E−02 5.43E−03 1.77E−03 −1 FPGT NM_006299 1.74E−02 5.43E−03 4.66E−02 −1 ZNF193 AF082283 1.74E−02 2.19E−02 4.89E−02 −1 BCL10 NM_007309 1.74E−02 2.72E−02 1.60E−02 −1 DIAPH2 NM_020423 1.74E−02 2.72E−02 1.01E−02 −1 PACE-1 NM_012135 1.74E−02 2.19E−02 4.11E−03 −1 FAM50B NM_006300 1.74E−02 2.72E−02 3.98E−02 −1 ZNF230 NM_006588 1.74E−02 2.19E−02 5.41E−03 −1 HSGP25L2G NM_003265 1.74E−02 2.72E−02 4.50E−02 −1 TLR3 NM_002158 1.74E−02 2.19E−02 1.63E−03 −1 HTLF NM_001499 1.74E−02 2.72E−02 1.35E−02 −1 GLE1L NM_000647 1.74E−02 5.47E−04 8.05E−04 −1 CCR2 NM_004858 1.74E−02 2.19E−02 1.38E−03 −1 SLC4A8 NM_015384 1.74E−02 5.47E−04 3.22E−03 −1 NIPBL NM_003438 1.74E−02 5.47E−04 4.76E−04 −1 ZNF137 NM_024986 1.74E−02 2.19E−02 9.65E−03 −1 FLJ12331 NM_014812 1.74E−02 5.43E−03 3.21E−03 −1 KAB NM_017522 1.74E−02 2.19E−02 4.19E−02 −1 LRP8 NM_004324 1.74E−02 2.72E−02 3.10E−02 −1 BAX AK024823 1.74E−02 2.19E−02 4.04E−03 −1 SUMO2 AL570661 1.74E−02 2.72E−02 8.23E−03 −1 MCP U72937 1.74E−02 2.19E−02 3.01E−02 −1 ATRX AW073672 1.74E−02 5.43E−03 3.21E−03 −1 CTNND1 BG534245 1.74E−02 4.17E−03 2.31E−03 −1 CSNK1A1 AI659005 1.74E−02 7.75E−03 2.60E−03 −1 LGALS8 BC005374 1.74E−02 2.19E−02 4.87E−02 −1 TXNDC4 AF208043 1.74E−02 1.18E−02 2.83E−04 −1 IFI16 BC002719 1.74E−02 2.72E−02 1.91E−02 −1 EIF3S1 AF247168 1.74E−02 2.43E−02 3.04E−02 −1 NPD014 AF006516 1.74E−02 2.19E−02 5.99E−03 −1 ABI1 NM_001253 1.74E−02 1.18E−02 3.54E−03 −1 CDC5L BC003600 1.74E−02 2.19E−02 8.59E−03 −1 LMO4 AV701283 1.74E−02 2.19E−02 3.30E−03 −1 SEC22L1 AI753638 1.74E−02 2.19E−02 2.93E−02 −1 OSBPL2 AF165513 1.74E−02 2.19E−02 4.41E−03 −1 VPS45A AF008442 1.74E−02 2.19E−02 8.61E−03 −1 POLR1C AF112207 1.74E−02 2.19E−02 1.73E−03 −1 — BE963245 1.74E−02 2.19E−02 4.82E−03 −1 FBXW11 N25915 1.74E−02 2.72E−02 1.41E−02 −1 CUGBP1 AK001280 1.74E−02 2.19E−02 2.35E−02 −1 HDGFRP3 AL133600 1.74E−02 5.47E−04 1.41E−03 −1 STAM2 AF182198 1.74E−02 2.72E−02 8.03E−03 −1 ITSN2 AF176699 1.74E−02 2.72E−02 5.37E−03 −1 FBXL4 U22815 1.74E−02 2.19E−02 1.20E−02 −1 PPFIA1 BC001265 1.74E−02 2.19E−02 3.12E−03 −1 DJ462O23.2 U89358 1.74E−02 2.19E−02 3.57E−02 −1 L3MBTL AB034951 1.74E−02 2.72E−02 4.79E−02 −1 HSPA8 BC002635 1.74E−02 2.19E−02 4.32E−02 −1 CSF2RA AF274935 1.74E−02 2.19E−02 9.75E−03 −1 LOC54499 BC005259 1.74E−02 2.19E−02 8.41E−03 −1 XRCC4 AB002382 1.74E−02 2.19E−02 4.24E−03 −1 CTNND1 BC006181 1.74E−02 2.19E−02 1.59E−02 −1 SFRS1 AI359472 1.74E−02 2.19E−02 9.72E−03 −1 XTP2 M27487 1.74E−02 2.72E−02 3.95E−02 −1 HLA-DPA1 AU143855 1.74E−02 2.72E−02 2.08E−02 −1 PSME4 BG111260 1.74E−02 2.19E−02 3.20E−03 −1 HIPK1 AK022910 1.74E−02 5.43E−03 4.83E−04 −1 TNPO3 AA195936 1.74E−02 5.43E−03 2.79E−02 −1 MGC21416 AV715767 1.74E−02 2.19E−02 1.14E−02 −1 LIM AV745949 1.74E−02 2.72E−02 2.35E−02 −1 SCAMP1 D26069 1.74E−02 2.72E−02 1.34E−02 −1 CENTB2 AL080111 1.74E−02 2.19E−02 1.71E−02 −1 NEK7 AL562282 1.74E−02 2.19E−02 4.97E−02 −1 PP591 BF970829 1.74E−02 2.19E−02 5.55E−03 −1 OSBPL8 AI991252 1.74E−02 2.19E−02 2.36E−02 −1 BTN3A2 AI742305 1.74E−02 4.17E−03 9.52E−05 −1 CHD9 AA524345 1.74E−02 2.19E−02 1.02E−02 −1 SNX4 AI752257 1.74E−02 2.72E−02 5.98E−03 −1 ZNF3 BG548738 1.74E−02 2.72E−02 1.08E−02 −1 KIAA1040 AB020684 1.74E−02 2.19E−02 1.15E−02 −1 KIAA0877 AI040324 1.74E−02 2.19E−02 2.72E−03 −1 NCOA2 AA284075 1.74E−02 2.72E−02 3.24E−03 −1 KNS2 BE786164 1.74E−02 7.75E−03 2.14E−03 −1 — AP000693 1.74E−02 1.18E−02 2.00E−03 −1 ZCWCC3 N22548 1.74E−02 2.19E−02 1.10E−03 −1 — BF970253 1.74E−02 2.19E−02 2.64E−02 −1 FLJ11806 AV682436 1.74E−02 5.43E−03 1.97E−03 −1 PIK3C2A Z78330 1.74E−02 5.43E−03 5.22E−03 −1 ACTR3 AI041204 1.74E−02 5.47E−04 3.79E−03 −1 CAP350 AL162056 1.74E−02 2.19E−02 4.90E−02 −1 KIAA1117 AI823592 1.74E−02 1.18E−02 3.18E−03 −1 KIAA0423 AI989567 1.74E−02 2.19E−02 3.94E−02 −1 SIAT10 BF223370 1.74E−02 2.72E−02 2.52E−02 −1 MGC11332 AW190088 1.74E−02 2.72E−02 3.63E−02 −1 ZNF307 AI655015 1.74E−02 2.72E−02 1.05E−02 −1 DUSP7 AA053830 1.74E−02 2.72E−02 3.29E−02 −1 CTBP1 BE501352 1.74E−02 2.72E−02 9.70E−03 −1 DKFZp667G2110 AB011097 1.74E−02 2.19E−02 9.50E−03 −1 ARTS-1 M19720 1.74E−02 4.17E−03 1.92E−03 −1 — AI912583 1.74E−02 4.17E−03 2.31E−03 −1 HRB2 AA890010 1.74E−02 2.19E−02 1.46E−02 −1 — AI376724 1.74E−02 5.43E−03 5.94E−04 −1 COX11 AA209332 1.74E−02 2.19E−02 2.04E−02 −1 OPA1 N58120 1.74E−02 2.19E−02 6.36E−03 −1 — M34356 1.74E−02 2.19E−02 4.08E−02 −1 CREB1 AK026142 1.74E−02 5.43E−03 4.71E−04 −1 ODAG AI357539 1.74E−02 4.17E−03 1.80E−03 −1 LRCH3 AI571996 1.74E−02 2.19E−02 3.71E−02 −1 STAM2 AA830884 1.74E−02 2.19E−02 9.07E−03 −1 FMR1 AA573862 1.74E−02 2.72E−02 2.11E−02 −1 HLA-A AL121936 1.74E−02 7.75E−03 2.66E−03 −1 BTN2A1 AC005614 1.74E−02 2.43E−02 2.52E−03 −1 LOC163131 /// LOC284323 AL163248 1.74E−02 2.19E−02 1.33E−02 −1 ZNF294 AK024456 1.74E−02 5.47E−04 5.10E−03 −1 FGD2 AK001861 1.74E−02 4.17E−03 5.47E−04 −1 SNX13 AK025663 1.74E−02 5.43E−03 1.00E−02 −1 ZNF291 AK024606 1.74E−02 5.43E−03 1.73E−03 −1 — AK025097 1.74E−02 2.19E−02 4.60E−02 −1 — AF035299 1.74E−02 5.47E−04 5.00E−03 −1 DOK1 X69383 1.74E−02 2.43E−02 1.30E−02 −1 — S67289 1.74E−02 5.43E−03 3.46E−03 −1 CYBB AI339732 1.74E−02 1.21E−03 1.55E−03 −1 CIAO1 AA719797 1.74E−02 2.19E−02 4.46E−02 −1 OR7E18P NM_014052 1.74E−02 2.19E−02 1.90E−03 −1 YWHAB NM_014426 1.74E−02 2.72E−02 6.25E−03 −1 SNX5 NM_018184 1.74E−02 4.17E−03 7.32E−03 −1 ARL10C NM_016166 1.74E−02 2.19E−02 1.59E−02 −1 PIAS1 NM_018442 1.74E−02 2.19E−02 2.87E−02 −1 IQWD1 NM_018244 1.74E−02 2.19E−02 4.15E−02 −1 C20orf44 NM_015153 1.74E−02 2.19E−02 1.15E−02 −1 PHF3 NM_015961 1.74E−02 2.72E−02 3.91E−03 −1 SNF7DC2 NM_018361 1.74E−02 2.19E−02 1.76E−02 −1 LPAAT-e BC005316 1.74E−02 2.72E−02 4.18E−02 −1 NFYB NM_018229 1.74E−02 2.19E−02 1.59E−02 −1 C14orf108 AF195514 1.74E−02 5.47E−04 9.81E−04 −1 VPS4B NM_024573 1.74E−02 5.43E−03 3.35E−03 −1 C6orf211 NM_014028 1.74E−02 2.19E−02 4.90E−02 −1 OSTM1 NM_001668 1.74E−02 2.19E−02 3.53E−02 −1 ARNT NM_022494 1.74E−02 2.19E−02 9.09E−03 −1 ZDHHC6 NM_022776 1.74E−02 5.47E−04 8.77E−04 −1 OSBPL11 NM_022067 1.74E−02 2.19E−02 1.91E−02 −1 C14orf133 NM_020640 1.74E−02 2.19E−02 1.07E−02 −1 RP42 NM_018115 1.74E−02 1.18E−02 8.56E−04 −1 SDAD1 NM_017646 1.74E−02 2.19E−02 9.56E−04 −1 TRIT1 NM_003929 1.74E−02 2.72E−02 2.23E−02 −1 RAB7L1 NM_017850 1.74E−02 7.75E−03 1.01E−03 −1 FLJ20508 NM_012123 1.74E−02 2.72E−02 2.21E−02 −1 MTO1 AK024569 1.74E−02 5.43E−03 1.05E−02 −1 HSPC163 NM_023010 1.74E−02 2.19E−02 2.12E−03 −1 UPF3B NM_025080 1.74E−02 5.43E−03 5.58E−03 −1 ASRGL1 NM_017810 1.74E−02 2.72E−02 1.59E−02 −1 ZNF434 NM_018569 1.74E−02 2.19E−02 8.22E−03 −1 C4orf16 NM_019083 1.74E−02 2.72E−02 2.38E−02 −1 FLJ10287 AF119868 1.74E−02 5.43E−03 1.89E−02 −1 KIAA1922 NM_016020 1.74E−02 2.19E−02 1.58E−02 −1 TFB1M NM_024638 1.74E−02 1.21E−03 1.92E−03 −1 QTRTD1 NM_022168 1.74E−02 2.72E−02 9.45E−03 −1 IFIH1 NM_024828 1.74E−02 2.19E−02 1.58E−03 −1 C9orf82 NM_024546 1.74E−02 2.19E−02 1.30E−02 −1 C13orf7 NM_017912 1.74E−02 2.72E−02 4.68E−02 −1 HERC6 NM_017687 1.74E−02 2.19E−02 2.54E−03 −1 NHLRC2 NM_024862 1.74E−02 7.75E−03 4.33E−03 −1 FBXO38 NM_025027 1.74E−02 2.72E−02 3.08E−02 −1 ZNF606 NM_025231 1.74E−02 4.17E−03 1.49E−03 −1 ZNF435 NM_022147 1.74E−02 2.19E−02 3.26E−02 −1 IFRG28 NM_004923 1.74E−02 2.72E−02 1.87E−02 −1 MTL5 NM_024838 1.74E−02 5.43E−03 1.90E−02 −1 — NM_024833 1.74E−02 2.19E−02 3.46E−02 −1 FLJ23506 NM_007210 1.74E−02 1.21E−03 2.38E−03 −1 GALNT6 NM_005774 1.74E−02 2.43E−02 2.15E−02 −1 ZNF224 NM_016424 1.74E−02 2.19E−02 4.40E−03 −1 CROP NM_018372 1.74E−02 2.72E−02 3.91E−02 −1 RIF1 NM_013240 1.74E−02 2.19E−02 2.64E−03 −1 C21orf127 NM_018327 1.74E−02 5.43E−03 2.08E−02 −1 C20orf38 NM_015510 1.74E−02 2.72E−02 1.83E−02 −1 DKFZp566O084 NM_018976 1.74E−02 5.43E−03 8.66E−03 −1 SLC38A2 NM_030917 1.74E−02 2.19E−02 1.22E−02 −1 FIP1L1 NM_030911 1.74E−02 1.21E−03 4.68E−04 −1 CDADC1 NM_030963 1.74E−02 5.43E−03 1.52E−02 −1 RNF146 AL120704 1.74E−02 2.19E−02 3.01E−02 −1 KPNA3 BC000039 1.74E−02 1.21E−03 6.70E−04 −1 FAM26B AF257135 1.74E−02 2.19E−02 3.46E−02 −1 WBSCR5 AF274950 1.74E−02 5.43E−03 4.34E−02 −1 FLJ10637 BC003073 1.74E−02 5.43E−03 1.21E−03 −1 FLJ10521 AL565516 1.74E−02 2.19E−02 2.11E−02 −1 PANK3 AI433464 1.74E−02 2.19E−02 3.87E−02 −1 PGM3 NM_004251 1.74E−02 2.19E−02 3.14E−02 −1 RAB9A AW162015 1.74E−02 2.72E−02 6.39E−03 −1 ZNF143 AW002578 1.74E−02 2.19E−02 3.05E−02 −1 MGC3731 AI983115 1.74E−02 2.72E−02 9.07E−03 −1 IL27RA AW008921 1.74E−02 2.19E−02 3.59E−02 −1 SENP5 AL137398 1.74E−02 2.72E−02 2.16E−03 −1 DKFZp434P162 R43279 1.74E−02 4.17E−03 1.74E−03 −1 SNAPC3 AW975638 1.74E−02 2.19E−02 4.47E−02 −1 — AF070618 1.74E−02 2.19E−02 1.09E−02 −1 MRPS22 U07139 1.74E−02 2.19E−02 4.38E−02 −1 CACNB3 D29642 1.74E−02 5.47E−04 1.84E−02 −1 ARHGAP25 AI458463 1.74E−02 5.43E−03 9.08E−03 −1 PACE-1 Z48481 3.95E−02 2.49E−02 2.75E−02 −1 MMP14 AV702810 3.95E−02 2.49E−02 6.09E−03 −1 SET NM_016451 3.95E−02 4.88E−03 4.12E−03 −1 COPB AF205218 3.95E−02 2.52E−03 1.02E−03 −1 IVNS1ABP AW968555 3.95E−02 3.54E−02 4.32E−02 −1 TBL1X NM_007214 3.95E−02 3.54E−02 3.59E−03 −1 SEC63 NM_006838 3.95E−02 4.91E−02 1.87E−02 −1 — BC000603 3.95E−02 3.54E−02 3.10E−03 −1 — BE250417 3.95E−02 4.91E−02 9.76E−03 −1 ZMYND11 AW183478 3.95E−02 9.26E−03 1.65E−02 −1 STK17A NM_015641 3.95E−02 2.49E−02 1.28E−02 −1 TES NM_014872 3.95E−02 4.91E−02 2.61E−02 −1 ZBTB5 NM_014753 3.95E−02 4.91E−02 2.64E−02 −1 BMS1L NM_001482 3.95E−02 9.26E−03 7.96E−03 −1 GATM NM_000702 3.95E−02 2.49E−02 5.02E−03 −1 ATP1A2 NM_006214 3.95E−02 3.54E−02 3.50E−02 −1 PHYH BG034328 3.95E−02 4.88E−03 5.06E−03 −1 TFDP2 BG252490 3.95E−02 4.91E−02 2.36E−02 −1 DNAJB4 NM_016024 3.95E−02 4.91E−02 3.39E−02 −1 RBMX2 NM_001353 3.95E−02 2.32E−02 6.14E−03 −1 AKR1C1 NM_000428 3.95E−02 2.49E−02 1.45E−02 −1 LTBP2 BF224146 3.95E−02 4.91E−02 3.64E−03 −1 TMEM5 NM_002830 3.95E−02 3.54E−02 2.79E−02 −1 PTPN4 NM_021077 3.95E−02 4.91E−02 4.77E−02 −1 NMB NM_004944 3.95E−02 1.23E−02 3.94E−03 −1 DNASE1L3 NM_016352 3.95E−02 9.26E−03 1.01E−02 −1 CPA4 NM_003151 3.95E−02 3.54E−02 1.24E−02 −1 STAT4 NM_002649 3.95E−02 3.54E−02 2.51E−02 −1 PIK3CG NM_024506 3.95E−02 4.91E−02 1.05E−02 −1 GLB1L NM_016436 3.95E−02 1.23E−02 2.13E−03 −1 C20orf104 NM_001240 3.95E−02 2.32E−02 5.79E−03 −1 CCNT1 NM_006610 3.95E−02 2.32E−02 3.17E−02 −1 MASP2 NM_002385 3.95E−02 3.54E−02 4.24E−02 −1 MBP BG494940 3.95E−02 4.91E−02 1.96E−02 −1 SSA2 NM_014257 3.95E−02 1.75E−02 6.26E−03 −1 CD209L NM_007068 3.95E−02 3.54E−02 3.77E−02 −1 DMC1 AF208850 3.95E−02 4.91E−02 1.60E−02 −1 PTP4A2 AF116710 3.95E−02 1.75E−02 9.09E−03 −1 RPS14 BC001019 3.95E−02 1.23E−02 1.21E−02 −1 RPL39 BC000734 3.95E−02 4.58E−02 1.57E−02 −1 EIF3S6 AF226044 3.95E−02 4.91E−02 4.07E−02 −1 SNRK AY008372 3.95E−02 3.54E−02 2.90E−02 −1 OSBPL3 AF271775 3.95E−02 3.54E−02 5.26E−03 −1 LAT1-3TM U79526 3.95E−02 3.54E−02 2.21E−02 −1 CMKLR1 AF031137 3.95E−02 3.54E−02 9.11E−03 −1 NCR3 AB006589 3.95E−02 2.49E−02 3.80E−02 −1 ESR2 AF000381 3.95E−02 4.58E−02 9.92E−03 −1 — BE466128 3.95E−02 3.54E−02 2.57E−02 −1 RBM25 AI631874 3.95E−02 3.54E−02 7.58E−03 −1 CSNK2A1 BG403834 3.95E−02 2.49E−02 2.54E−02 −1 KPNA6 AW593213 3.95E−02 1.23E−02 1.83E−03 −1 KIAA1078 BF214492 3.95E−02 7.66E−04 3.51E−03 −1 RPL5 AA521269 3.95E−02 4.58E−02 1.11E−02 −1 — BF739959 3.95E−02 1.23E−02 1.31E−02 −1 MFHAS1 AW302047 3.95E−02 4.91E−02 6.80E−03 −1 — AI252582 3.95E−02 2.49E−02 1.10E−03 −1 — AI539361 3.95E−02 1.23E−02 1.39E−02 −1 — NM_012081 3.95E−02 4.58E−02 1.28E−02 −1 ELL2 AA400421 3.95E−02 4.91E−02 2.82E−02 −1 TWISTNB AK023851 3.95E−02 4.88E−03 1.60E−03 −1 CAPN2 BE000837 3.95E−02 1.23E−02 1.96E−03 −1 KIAA0220 AL121891 3.95E−02 3.54E−02 3.37E−03 −1 UBCE7IP5 AK023621 3.95E−02 9.26E−03 1.74E−02 −1 RHOBTB3 S69182 3.95E−02 4.88E−03 3.02E−03 −1 — AK026521 3.95E−02 3.54E−02 6.64E−03 −1 TAF1B AL354872 3.95E−02 3.54E−02 4.77E−02 −1 CTH NM_022731 3.95E−02 4.88E−03 4.52E−03 −1 NUCKS NM_020239 3.95E−02 3.54E−02 1.25E−02 −1 CDC42SE1 NM_022365 3.95E−02 3.54E−02 2.20E−02 −1 DNAJC1 AV682567 3.95E−02 3.54E−02 4.39E−02 −1 MDS010 NM_024779 3.95E−02 2.49E−02 2.19E−02 −1 PIP5K2C NM_016052 3.95E−02 4.88E−03 2.26E−03 −1 CGI-115 NM_022073 3.95E−02 4.91E−02 4.41E−02 −1 EGLN3 NM_013281 3.95E−02 2.49E−02 3.12E−02 −1 FLRT3 NM_016122 3.95E−02 3.54E−02 9.15E−03 −1 NY-REN-58 NM_024084 3.95E−02 2.49E−02 8.27E−03 −1 MGC3196 NM_017860 3.95E−02 3.54E−02 3.82E−03 −1 FLJ20519 NM_023034 3.95E−02 2.32E−02 1.26E−02 −1 WHSC1L1 NM_002548 3.95E−02 2.49E−02 2.42E−02 −1 OR1D2 AL136733 3.95E−02 4.91E−02 1.29E−02 −1 UBAP1 BC005934 3.95E−02 2.32E−02 1.83E−03 −1 FLJ21168 AW303136 3.95E−02 4.88E−03 2.28E−03 −1 — W87634 3.95E−02 2.49E−02 6.65E−03 −1 CXorf33 AI669379 3.95E−02 4.91E−02 1.28E−02 −1 — BG025063 3.95E−02 3.54E−02 3.63E−02 −1 — NM_014622 1.49E−04 1.49E−04 2.75E−03 1 LOH11CR2A M87268 1.49E−04 1.49E−04 1.71E−03 1 IGHG1 NM_024588 1.49E−04 1.49E−04 4.18E−03 1 FLJ23584 NM_030926 1.49E−04 3.72E−05 2.14E−04 1 ITM2C NM_021173 2.70E−04 2.34E−04 1.25E−04 1 POLD4 NM_014403 2.70E−04 4.40E−04 1.20E−04 1 SIAT7D NM_004930 1.82E−03 9.10E−04 8.75E−04 1 CAPZB AF129756 1.82E−03 2.96E−03 1.39E−02 1 BAT2 AL096733 1.82E−03 2.96E−03 2.18E−03 1 ATP6V0A1 W74620 1.82E−03 1.47E−03 8.07E−04 1 HNRPD AC002544 1.82E−03 1.79E−03 2.14E−02 1 LOC283970 AF008937 1.82E−03 8.95E−05 4.76E−06 1 STX16 NM_006284 2.01E−03 2.88E−03 3.75E−02 1 TAF10 BF969352 2.01E−03 2.88E−03 6.33E−04 1 ECE1 AA675892 2.01E−03 1.69E−03 9.55E−04 1 TOB1 NM_004395 2.01E−03 2.88E−03 1.56E−02 1 DBN1 NM_000558 2.01E−03 2.88E−03 1.18E−03 1 HBA1 /// HBA2 NM_002412 2.01E−03 2.88E−03 2.62E−03 1 MGMT NM_003955 2.01E−03 1.69E−03 3.20E−02 1 SOCS3 NM_004089 2.01E−03 1.69E−03 4.98E−04 1 DSIPI AF022231 2.01E−03 2.88E−03 2.04E−03 1 CTDSP2 AL110191 2.01E−03 1.69E−03 4.57E−04 1 DSIPI M25079 2.01E−03 2.88E−03 1.68E−03 1 HBB L01639 2.01E−03 2.88E−03 5.25E−03 1 CXCR4 AF105974 2.01E−03 2.88E−03 1.36E−03 1 HBA1 /// HBA2 L07555 2.01E−03 2.88E−03 9.46E−03 1 CD69 AF167343 2.01E−03 2.88E−03 1.04E−02 1 IL1RAP AF116676 2.01E−03 2.88E−03 1.99E−02 1 MYL4 AF349114 2.01E−03 2.88E−03 1.56E−03 1 HBB AF349571 2.01E−03 2.88E−03 1.59E−03 1 HBA1 /// HBA2 BC005931 2.01E−03 2.88E−03 1.33E−03 1 HBA1 AJ225092 2.01E−03 2.88E−03 5.25E−03 1 IGHG1 AF348491 2.01E−03 2.88E−03 7.22E−03 1 CXCR4 T50399 2.01E−03 2.88E−03 1.29E−03 1 HBA2 AJ275355 2.01E−03 1.21E−03 5.42E−04 1 MGC27165 AJ249377 2.01E−03 2.88E−03 5.89E−03 1 IGLJ3 AF059180 2.01E−03 2.88E−03 1.99E−03 1 HBB AJ275374 2.01E−03 1.69E−03 3.02E−03 1 — V00489 2.01E−03 2.88E−03 1.63E−03 1 HBA2 NM_024299 2.01E−03 1.69E−03 1.98E−02 1 C20orf149 NM_020360 2.01E−03 1.69E−03 3.92E−03 1 PLSCR3 NM_017679 2.01E−03 1.21E−03 1.93E−04 1 BCAS3 AF230924 2.01E−03 2.88E−03 6.68E−03 1 C6orf82 AA523441 2.01E−03 2.88E−03 6.97E−04 1 PEX16 NM_005186 9.49E−03 1.56E−02 1.12E−02 1 CAPN1 BF304759 9.49E−03 7.52E−03 3.75E−02 1 LRP1 NM_001662 9.49E−03 8.40E−03 4.40E−03 1 ARF5 AF113019 9.49E−03 7.52E−03 3.36E−03 1 SMARCD2 NM_003025 9.49E−03 7.52E−03 2.68E−02 1 SH3GL1 NM_014846 9.49E−03 1.37E−02 4.68E−02 1 KIAA0196 NM_017458 9.49E−03 1.23E−02 2.56E−03 1 MVP NM_006243 9.49E−03 1.56E−02 4.40E−02 1 PPP2R5A NM_001985 9.49E−03 1.56E−02 3.40E−02 1 ETFB NM_016621 9.49E−03 1.37E−02 3.12E−02 1 BHC80 NM_004565 9.49E−03 1.23E−02 1.37E−03 1 PEX14 NM_005509 9.49E−03 1.56E−02 1.43E−02 1 DMXL1 NM_005224 9.49E−03 9.26E−03 8.52E−03 1 ARID3A NM_003070 9.49E−03 1.56E−02 1.21E−02 1 SMARCA2 AI810484 9.49E−03 3.63E−04 4.25E−03 1 CBFA2T2 AF226990 9.49E−03 1.37E−02 2.39E−02 1 HLA-G U78774 9.49E−03 7.52E−03 1.03E−02 1 NFYC U71088 9.49E−03 3.63E−04 1.69E−03 1 MAP2K5 AA085748 9.49E−03 1.56E−02 1.69E−02 1 LOC149603 AB011126 9.49E−03 8.40E−03 2.72E−03 1 FNBP1 BF570210 9.49E−03 1.37E−02 4.19E−03 1 PNPLA2 AI343248 9.49E−03 1.37E−02 7.03E−03 1 SRP46 AA126728 9.49E−03 7.52E−03 2.86E−02 1 ICAM2 N36926 9.49E−03 8.40E−03 1.13E−02 1 GNA11 AA602532 9.49E−03 8.40E−03 1.41E−02 1 CLN2 BE898639 9.49E−03 8.40E−03 1.18E−02 1 ADD1 AV724215 9.49E−03 1.56E−02 2.07E−02 1 — AK001574 9.49E−03 1.37E−02 3.28E−03 1 GORASP1 BF034906 9.49E−03 8.40E−03 2.75E−03 1 PL6 AL121981 9.49E−03 3.33E−03 1.69E−03 1 DLG1 NM_024531 9.49E−03 7.52E−03 1.12E−02 1 GPR172A NM_016274 9.49E−03 8.40E−03 1.75E−03 1 CKIP-1 NM_004542 9.49E−03 7.52E−03 1.25E−02 1 NDUFA3 NM_007254 9.49E−03 1.37E−02 4.31E−03 1 PNKP NM_015711 9.49E−03 1.37E−02 1.96E−03 1 GLTSCR1 NM_022350 9.49E−03 1.56E−02 4.57E−02 1 LRAP NM_017915 9.49E−03 1.56E−02 3.46E−02 1 FLJ20641 AK026970 9.49E−03 7.52E−03 1.53E−03 1 STX16 AF078847 9.49E−03 1.37E−02 3.27E−02 1 GTF2H2 AI828531 9.49E−03 1.56E−02 1.01E−02 1 WIZ NM_001344 1.74E−02 2.19E−02 2.80E−02 1 DAD1 NM_006184 1.74E−02 2.19E−02 3.03E−03 1 NUCB1 NM_002743 1.74E−02 2.19E−02 8.32E−03 1 PRKCSH NM_007245 1.74E−02 2.43E−02 3.73E−03 1 ATXN2L NM_015853 1.74E−02 2.19E−02 7.03E−03 1 LOC51035 NM_003367 1.74E−02 2.72E−02 3.92E−02 1 USF2 NM_025195 1.74E−02 2.19E−02 4.92E−03 1 TRIB1 BE675849 1.74E−02 2.19E−02 4.29E−02 1 C9orf60 BC000436 1.74E−02 2.19E−02 1.14E−02 1 ENSA NM_006732 1.74E−02 2.19E−02 1.84E−02 1 FOSB NM_019058 1.74E−02 2.72E−02 1.70E−02 1 DDIT4 NM_020248 1.74E−02 2.19E−02 2.01E−02 1 CTNNBIP1 NM_003364 1.74E−02 2.72E−02 3.03E−02 1 UPP1 NM_016294 1.74E−02 2.19E−02 9.73E−03 1 PPP6C NM_014569 1.74E−02 2.19E−02 1.31E−02 1 ZFP95 NM_005354 1.74E−02 2.72E−02 3.91E−02 1 JUND NM_004994 1.74E−02 2.72E−02 3.80E−03 1 MMP9 NM_021127 1.74E−02 2.19E−02 4.47E−02 1 PMAIP1 NM_002460 1.74E−02 2.19E−02 4.63E−02 1 IRF4 NM_002201 1.74E−02 2.72E−02 3.88E−03 1 ISG20 NM_004073 1.74E−02 2.19E−02 1.47E−02 1 PLK3 NM_005738 1.74E−02 2.19E−02 4.15E−02 1 ARL4A NM_014716 1.74E−02 2.19E−02 1.32E−02 1 CENTB1 BG035761 1.74E−02 5.43E−03 1.26E−02 1 SOCS3 NM_018134 1.74E−02 2.19E−02 3.27E−02 1 IQCC NM_000519 1.74E−02 2.19E−02 2.23E−02 1 HBD NM_003811 1.74E−02 1.18E−02 1.57E−02 1 TNFSF9 NM_005191 1.74E−02 2.19E−02 8.99E−03 1 CD80 NM_017528 1.74E−02 4.17E−03 9.17E−04 1 WBSCR22 NM_002620 1.74E−02 2.72E−02 4.54E−02 1 PF4V1 NM_000423 1.74E−02 2.19E−02 7.31E−04 1 KRT2A AL578551 1.74E−02 2.19E−02 4.25E−03 1 RNF10 U91543 1.74E−02 2.72E−02 1.55E−02 1 CHD3 BC004242 1.74E−02 2.19E−02 6.76E−03 1 HNRPUL1 U03886 1.74E−02 2.72E−02 2.05E−02 1 PNPLA4 M36172 1.74E−02 2.19E−02 3.03E−02 1 MYL4 U20498 1.74E−02 2.19E−02 6.66E−03 1 CDKN2D BC000383 1.74E−02 4.17E−03 3.83E−02 1 WTAP BC006383 1.74E−02 5.43E−03 4.42E−04 1 GPAA1 AY026505 1.74E−02 5.43E−03 8.99E−04 1 KIF2C U17074 1.74E−02 2.19E−02 1.23E−02 1 CDKN2C D87858 1.74E−02 2.19E−02 3.94E−02 1 FCAR AI827941 1.74E−02 5.43E−03 1.32E−03 1 MYH9 BE968833 1.74E−02 2.72E−02 2.71E−02 1 SPTBN1 AK021419 1.74E−02 2.19E−02 2.12E−02 1 SMARCB1 D50918 1.74E−02 5.43E−03 3.23E−03 1 H65865 1.74E−02 2.72E−02 1.69E−02 1 FLJ13910 M62324 1.74E−02 5.43E−03 7.50E−03 1 ARID5A AW168132 1.74E−02 2.19E−02 3.40E−03 1 KIAA0404 AA514622 1.74E−02 2.19E−02 3.47E−02 1 POM121 /// LOC340318 AL578583 1.74E−02 5.47E−04 1.21E−03 1 CORT AA022949 1.74E−02 2.19E−02 1.18E−02 1 — BG485135 1.74E−02 2.72E−02 1.23E−02 1 — BG540628 1.74E−02 2.19E−02 1.73E−02 1 — BG482805 1.74E−02 2.19E−02 1.53E−02 1 — AC007842 1.74E−02 2.19E−02 4.29E−02 1 LOC163131 BG325734 1.74E−02 2.72E−02 1.53E−02 1 MAPKAPK2 AW404894 1.74E−02 2.72E−02 1.37E−02 1 — W46388 1.74E−02 2.72E−02 1.58E−02 1 SOD2 AL008730 1.74E−02 4.17E−03 3.33E−03 1 C6orf4 X58851 1.74E−02 2.19E−02 4.04E−02 1 MYL4 L14482 1.74E−02 2.19E−02 2.57E−02 1 POU6F1 AL050332 1.74E−02 2.19E−02 1.57E−03 1 LYPLA2P1 D84143 1.74E−02 2.19E−02 5.78E−03 1 — AJ224869 1.74E−02 2.19E−02 7.85E−03 1 CXCR4 AL022067 1.74E−02 2.72E−02 2.51E−02 1 PRDM1 AL512687 1.74E−02 5.43E−03 1.56E−03 1 NOMO2 /// NOMO1 /// NOMO3 D84140 1.74E−02 2.19E−02 4.15E−03 1 — AF043583 1.74E−02 2.19E−02 1.59E−02 1 — AI042030 1.74E−02 5.43E−03 3.57E−03 1 SMC1L1 NM_005746 1.74E−02 2.72E−02 9.92E−03 1 PBEF1 NM_005746 1.74E−02 2.72E−02 1.28E−02 1 PBEF1 AL523965 1.74E−02 2.19E−02 1.86E−02 1 C6orf106 NM_017874 1.74E−02 2.19E−02 2.42E−03 1 C20orf27 NM_022452 1.74E−02 5.43E−03 1.14E−02 1 FBS1 NM_024324 1.74E−02 2.19E−02 2.83E−03 1 — NM_024535 1.74E−02 2.19E−02 1.05E−03 1 CORO7 NM_023948 1.74E−02 2.19E−02 1.92E−02 1 MOSPD3 NM_022341 1.74E−02 5.43E−03 1.97E−03 1 PDF /// COG8 NM_016633 1.74E−02 2.19E−02 2.74E−02 1 ERAF NM_012447 1.74E−02 2.72E−02 1.41E−02 1 STAG3 NM_020533 1.74E−02 2.19E−02 4.81E−02 1 MCOLN1 NM_019891 1.74E−02 2.19E−02 2.86E−02 1 ERO1LB NM_018113 1.74E−02 2.19E−02 4.51E−02 1 LIMR NM_017774 1.74E−02 5.43E−03 7.44E−03 1 CDKAL1 NM_024669 1.74E−02 2.72E−02 3.93E−03 1 FLJ11795 NM_014076 1.74E−02 7.75E−03 7.57E−04 1 GPR97 N39536 1.74E−02 5.43E−03 1.95E−03 1 NOMO2 /// NOMO1 /// NOMO3 L14754 1.74E−02 2.19E−02 2.49E−02 1 IGHMBP2 Y14330 1.74E−02 2.43E−02 4.44E−03 1 JAG2 U88964 1.74E−02 2.19E−02 1.28E−02 1 ISG20 AL096779 1.74E−02 2.72E−02 2.66E−02 1 C22orf4 AC005954 1.74E−02 4.17E−03 4.12E−03 1 TJP3 AF022991 1.74E−02 2.72E−02 1.02E−02 1 PER1 AB002328 1.74E−02 2.72E−02 1.88E−02 1 CABIN1 AI150117 1.74E−02 2.72E−02 1.52E−02 1 TOPORS AI743331 1.74E−02 2.19E−02 7.64E−03 1 C20orf67 L38487 3.95E−02 3.54E−02 1.21E−02 1 ESRRA BC002356 3.95E−02 4.58E−02 8.37E−03 1 NUCB1 NM_000177 3.95E−02 7.66E−04 3.31E−03 1 GSN NM_000018 3.95E−02 4.91E−02 1.50E−02 1 ACADVL NM_002332 3.95E−02 3.54E−02 2.62E−02 1 LRP1 AI920976 3.95E−02 3.54E−02 1.14E−02 1 RERE AL523776 3.95E−02 9.26E−03 1.65E−02 1 OTUB1 NM_003097 3.95E−02 4.91E−02 4.68E−02 1 SNURF /// SNRPN NM_006295 3.95E−02 7.66E−04 4.08E−03 1 VARS2 NM_001540 3.95E−02 2.49E−02 2.73E−02 1 HSPB1 NM_003040 3.95E−02 2.52E−03 5.86E−03 1 SLC4A2 NM_015049 3.95E−02 3.54E−02 5.05E−03 1 ALS2CR3 BC005003 3.95E−02 4.91E−02 2.77E−02 1 NFYC BC000120 3.95E−02 2.49E−02 1.09E−02 1 GTF2F1 NM_005334 3.95E−02 3.54E−02 1.79E−02 1 HCFC1 NM_004216 3.95E−02 3.54E−02 1.04E−02 1 DEDD NM_006700 3.95E−02 1.23E−02 8.01E−04 1 FLN29 NM_004514 3.95E−02 2.49E−02 2.54E−02 1 FOXK2 NM_005077 3.95E−02 3.54E−02 5.69E−03 1 TLE1 NM_005641 3.95E−02 4.91E−02 9.70E−03 1 TAF6 NM_003704 3.95E−02 7.66E−04 3.50E−03 1 C4orf8 NM_006547 3.95E−02 3.54E−02 2.21E−02 1 IMP-3 AL136771 3.95E−02 2.32E−02 2.43E−03 1 ELL NM_000265 3.95E−02 4.88E−03 2.45E−03 1 NCF1 NM_002555 3.95E−02 9.26E−03 2.18E−03 1 SLC22A18 NM_003043 3.95E−02 3.54E−02 2.64E−02 1 SLC6A6 NM_014813 3.95E−02 1.23E−02 3.47E−03 1 LRIG2 NM_001157 3.95E−02 4.88E−03 5.60E−03 1 ANXA11 NM_006865 3.95E−02 4.58E−02 1.11E−02 1 LILRA3 NM_004258 3.95E−02 7.66E−04 3.58E−02 1 IGSF2 AF052179 3.95E−02 3.54E−02 3.45E−02 1 ARF1 BE674658 3.95E−02 2.32E−02 2.24E−02 1 FLJ13052 BC003381 3.95E−02 3.54E−02 1.54E−03 1 KIAA0217 K02920 3.95E−02 9.26E−03 7.34E−03 1 GBA D87454 3.95E−02 4.91E−02 4.30E−02 1 KIAA0265 U66879 3.95E−02 1.75E−02 3.88E−03 1 BAD AB011179 3.95E−02 2.32E−02 3.44E−03 1 NCDN D37781 3.95E−02 4.91E−02 1.33E−02 1 PTPRJ U22815 3.95E−02 2.49E−02 2.64E−03 1 PPFIA1 U81802 3.95E−02 2.49E−02 7.85E−03 1 PIK4CB BC004516 3.95E−02 9.26E−03 4.07E−02 1 MAX AF056322 3.95E−02 2.49E−02 2.77E−02 1 SP100 AF234161 3.95E−02 4.91E−02 5.17E−03 1 CIZ1 U90940 3.95E−02 4.91E−02 4.23E−02 1 FCGR2C AL046054 3.95E−02 2.32E−02 1.78E−02 1 PTOV1 AI762552 3.95E−02 4.91E−02 9.59E−03 1 HNRPDL BF974389 3.95E−02 3.54E−02 7.94E−03 1 MTVR1 AW237172 3.95E−02 2.32E−02 2.21E−02 1 JMJD2B AA877910 3.95E−02 1.23E−02 3.15E−03 1 ATP2A3 AW157619 3.95E−02 9.26E−03 3.57E−03 1 CES2 AW451236 3.95E−02 2.49E−02 2.11E−02 1 TCEB3 BE856549 3.95E−02 3.54E−02 4.99E−02 1 KIAA0974 AW072388 3.95E−02 1.75E−02 4.60E−03 1 NCF1 AK025604 3.95E−02 3.54E−02 9.44E−03 1 M-RIP AL096741 3.95E−02 4.58E−02 5.49E−03 1 ASCC2 AK025271 3.95E−02 3.54E−02 4.30E−02 1 CHCHD3 AB035175 3.95E−02 2.32E−02 2.57E−03 1 IGHG1 NM_016145 3.95E−02 4.91E−02 1.95E−02 1 PTD008 BE891920 3.95E−02 2.49E−02 4.78E−02 1 ARPC4 NM_024293 3.95E−02 9.26E−03 3.73E−03 1 C2orf17 NM_014164 3.95E−02 3.54E−02 1.73E−03 1 FXYD5 AL561281 3.95E−02 3.54E−02 4.57E−02 1 MAP4K4 NM_006342 3.95E−02 3.54E−02 3.08E−02 1 TACC3 NM_017684 3.95E−02 3.54E−02 1.76E−02 1 VPS13C NM_022089 3.95E−02 2.32E−02 4.84E−03 1 HSA9947 NM_018053 3.95E−02 2.49E−02 2.04E−02 1 FLJ10307 NM_024604 3.95E−02 4.91E−02 3.07E−02 1 FLJ21908 NM_018694 3.95E−02 3.54E−02 4.96E−02 1 ARL6IP4 NM_019096 3.95E−02 4.58E−02 6.10E−03 1 GTPBP2 AB016531 3.95E−02 2.52E−03 1.67E−02 1 PEX16 AI660075 3.95E−02 3.54E−02 3.63E−02 1 LRCH4 AF052151 3.95E−02 4.88E−03 7.99E−03 1 MTVR1 AI744083 3.95E−02 3.54E−02 6.98E−03 1 MOSPD2 Table 4: Provided are genetic markers which are differentially expressed between subjects diagnosed with definite multiple sclerosis and healthy controls (the Probeset ID of the Affymetrix Gene Chip), along with the corresponding GenBank accession number (GenBank Acc. No.), the gene symbol and the direction (Dir) of change in gene expression (“1” - upregulation; “−1” - downregulation). Note that the p values of the TNOM, Info and t-Test statistical tests all passed the 95% confidence level.

Example 3 Identification of Genes which Expression Pattern is Characteristics to Probable Multiple Sclerosis Subjects which Further Convert to Definite Multiple Sclerosis

Probable vs. definite gene expression patterns—To identify genes which expression pattern, i.e., upregulation or downregulation is characteristics to probable multiple sclerosis subjects who further convert to definite multiple sclerosis (within a 2 years period), the PBMC expression pattern of genes differentially expressed between definite RRMS/healthy controls (722 genetic markers shown in Table 4, hereinabove) was compared to the expression pattern of probable MS who converted to definite MS (12 patients, converted within 2-years)/healthy controls (1517 genetic markers shown in Table 2, hereinabove).

This intersection disclosed 58 universal genes that characterize probable (who are predisposed to develop definite MS) and definite MS disease (FIG. 3 and Table 5, hereinbelow). This signature included MMP genes: MMP9, MMP14; antigen presenting genes like: B7-1 (CD80, CD28); T-cells receptor genes and neuron survival genes: SIP1, TCRγV.

TABLE 5 Universal expression pattern of markers common to subjects with probable MS diagnosis which later converted to definite diagnosis of MS and subjects with definite diagnosis of MS SEQ ID GenBank Fold Probeset NO: Accession No. Dir Change Gene Symbol 203335_at 1 NM_006214 −1 2.0 PHYH 216746_at 2 AK024606 −1 2.1 AK024606 217377_x_at 3 AF041811 −1 2.3 NTRK3 214274_s_at 4 AI860341 −1 2.4 ACAA1 204151_x_at 5 NM_001353 −1 2.6 AKR1C1 203468_at 6 NM_003674 −1 2.9 CDK10 218303_x_at 7 NM_016618 −1 2.9 LOC51315 204221_x_at 8 U16307 −1 2.9 HRB2 218129_s_at 9 BC005316 −1 3.1 NFYB 212073_at 10 AI631874 −1 3.2 CSNK2A1 218607_s_at 11 NM_018115 −1 3.2 SDAD1 206271_at 12 NM_003265 −1 3.4 TLR3 217908_s_at 13 NM_018442 −1 3.5 IQWD1 160020_at 14 Z48481 −1 3.7 MMP14 217381_s_at 15 X69383 −1 4.1 TCR 218349_s_at 16 AA824298 −1 4.8 FLJ10036 221007_s_at 17 NM_030917 −1 5.0 FIP1L1 218728_s_at 18 AK024569 −1 5.7 HSPC163 218096_at 19 NM_018361 −1 6.2 LPAAT-e 213980_s_at 20 AA053830 −1 6.4 CTBP1 222149_x_at 21 AL137398 −1 6.6 DKFZp434P162 221222_s_at 22 NM_017860 −1 6.8 FLJ20519 202660_at 23 AA834576 −1 8.1 ITPR2 210235_s_at 24 U22815 −1 8.3 PPFIA1 205540_s_at 25 NM_016656 −1 8.8 RRAGB 204682_at 26 NM_000428 −1 9.0 LTBP2 218859_s_at 27 NM_016649 −1 12.2 C20orf6 218699_at 28 NM_003929 −1 26.5 RAB7L1 205063_at 29 NM_003616 −1 31.3 SIP1 214085_x_at 30 AI912583 −1 66.8 HRB2 216399_s_at 31 AK025663 −1 82.9 ZNF291 219575_s_at 32 NM_022341 1 2.0 PDF, COG8 216330_s_at 33 L14482 1 2.1 POU6F1 203222_s_at 34 NM_005077 1 2.1 TLE1 203064_s_at 35 NM_004514 1 2.2 FOXK2 207176_s_at 36 NM_005191 1 2.2 CD80 213360_s_at 37 AA514622 1 2.2 POM121 205920_at 38 NM_003043 1 2.4 SLC6A6 206544_x_at 39 NM_003070 1 2.4 SMARCA2 218961_s_at 40 NM_007254 1 2.7 PNKP 201526_at 41 NM_001662 1 2.9 ARF5 203936_s_at 42 NM_004994 1 3.0 MMP9 207908_at 43 NM_000423 1 3.1 KRT2A 202942_at 44 NM_001985 1 3.3 ETFB 211696_x_at 45 AF349114 1 4.3 HBB 218037_at 46 NM_024293 1 4.9 C2orf17 209116_x_at 47 M25079 1 5.3 HBB 204018_x_at 48 NM_000558 1 6.4 HBA1, HBA2 200055_at 49 NM_006284 1 6.5 TAF10 202596_at 50 BC000436 1 6.6 ENSA 201827_at 51 AF113019 1 7.2 SMARCD2 214414_x_at 52 T50399 1 7.6 HBA2 202768_at 53 NM_006732 1 14.0 FOSB 215684_s_at 54 AL096741 1 14.9 ASCC2 212071_s_at 55 BE968833 1 21.8 SPTBN1 202111_at 56 NM_003040 1 28.8 SLC4A2 212413_at 57 D50918 1 105.1 D50918 209740_s_at 58 U03886 1 106.7 PNPLA4 Table 5: Genetic markers which are differentially expressed between probable multiple sclerosis which further developed definite diagnosis of MS and healthy controls are provided (the Probeset ID of the Affymetrix Gene Chip), along with the corresponding GenBank accession number, the gene symbol, the SEQ ID NO., the direction of change in gene expression (“1”- upregulation; “−1” - downregulation) and the fold change in subjects diagnosed with probable MS (who are predisposed to develop definite MS) as compared to healthy control (probable MS/healthy control). Note that the p values of the TNOM, Info and t-Test statistical tests all passed the 95% confidence level.

Determination of the prediction power of selected genes which differentiate between probable MS subjects who are predisposed to develop definite MS and healthy controls—To evaluate the power of each of the 58 differentiating genes (SEQ ID NOs:1-58) identified in this study to predict the predisposition of a probable MS subject to develop a definite MS diagnosis, the study sample of 40 probable patients was randomly divided into 80% of the subjects as a “training set” and 20% (to confirm) of the subjects as a “test set” and a model was build using the SVM based on RBF kernel. For each of the differentiating genes the predictability of the training set on the test set was computed and the average error following 25 permutations was calculated. Genes with the lowest average error were selected, then, for each selected gene, the remaining genes were added one after the other, by selecting the next gene such that the average error after 25 repeats of the group of genes including the new gene has the lowest average error as compared to the addition of another gene. This process was repeated 57 times for each additional gene added to the previous group of genes. The resulting average error for each gene combination is depicted in Table 6, hereinbelow, wherein the first gene in row number 1 (SEQ ID NO:4) exhibits the best predictive power (error average of “0.21”) as a single gene.

TABLE 6 Row SEQ Num- ID Gene Bank Error Gene ber NO: Probeset ID ID Average Symbol 1 4 214274_s_at AI860341 0.216363636 ACAA1 2 16 218349_s_at NM_017975 0.216363636 FLJ10036 3 5 204151_x_at NM_001353 0.247272727 AKR1C1 4 56 202111_at NM_003040 0.230909091 SLC4A2 5 20 213980_s_at AA053830 0.223636364 CTBP1 6 3 217377_x_at AF041811 0.158181818 NTRK3 7 1 203335_at NM_006214 0.169090909 PHYH 8 10 212073_at AI631874 0.176363636 CSNK2A1 9 57 212413_at D50918 0.169090909 6-Sep 10 24 210235_s_at U22815 0.194545455 PPFIA1 11 14 160020_at Z48481 0.214545455 MMP14 12 49 200055_at NM_006284 0.201818182 TAF10 13 13 217908_s_at NM_018442 0.181818182 PC326 14 37 213360_s_at AA514622 0.163636364 na 15 6 203468_at NM_003674 0.165454545 CDK10 16 47 209116_x_at M25079 0.158181818 HBB 17 50 202596_at BC000436 0.163636364 ENSA 18 21 222149_x_at AL137398 0.154545455 — 19 46 218037_at NM_024293 0.143636364 MGC3035 20 8 204221_x_at U16307 0.165454545 GLIPR1 21 26 204682_at NM_000428 0.174545455 LTBP2 22 2 216746_at AK024606 0.169090909 — 23 15 217381_s_at X69383 0.172727273 — 24 51 201827_at AF113019 0.167272727 SMARCD2 25 44 202942_at NM_001985 0.170909091 ETFB 26 19 218096_at NM_018361 0.167272727 LPAAT-e 27 17 221007_s_at NM_030917 0.176363636 FIP1L1 28 25 205540_s_at NM_016656 0.176363636 RRAGB 29 33 216330_s_at L14482 0.161818182 POU6F1 30 48 204018_x_at NM_000558 0.174545455 HBA1 31 36 207176_s_at NM_005191 0.161818182 CD80 32 34 203222_s_at NM_005077 0.158181818 TLE1 33 12 206271_at NM_003265 0.132727273 TLR3 34 29 205063_at NM_003616 0.136363636 SIP1 35 23 202660_at AA834576 0.132727273 — 36 11 218607_s_at NM_018115 0.150909091 FLJ10498 37 45 211696_x_at AF349114 0.149090909 HBB 38 53 202768_at NM_006732 0.16 FOSB 39 41 201526_at NM_001662 0.156363636 ARF5 40 40 218961_s_at NM_007254 0.130909091 PNKP 41 31 216399_s_at AK025663 0.154545455 ZNF291 42 58 209740_s_at U03886 0.143636364 DXS1283E 43 27 218859_s_at NM_016649 0.147272727 C20orf6 44 43 207908_at NM_000423 0.132727273 KRT2A 45 35 203064_s_at NM_004514 0.132727273 ILF1 46 30 214085_x_at AI912583 0.16 HRB2 47 52 214414_x_at T50399 0.156363636 HBA1 48 55 212071_s_at BE968833 0.147272727 SPTBN1 49 7 218303_x_at NM_016618 0.16 LOC51315 50 9 218129_s_at NM_006166 0.161818182 NFYB 51 42 203936_s_at NM_004994 0.167272727 MMP9 52 28 218699_at BG338251 0.145454545 RAB7L1 53 54 215684_s_at AL096741 0.170909091 FLJ21588 54 32 219575_s_at NM_022341 0.167272727 COG8 55 22 221222_s_at NM_017860 0.178181818 FLJ20519 56 18 218728_s_at NM_014184 0.181818182 HSPC163 57 38 205920_at NM_003043 0.190909091 SLC6A6 58 39 206544_x_at NM_003070 0.194545455 SMARCA2 Table 6: Shown are the average errors of predicting a probability of a probable MS subject to develop the diagnosis of definite MS within a 2-years period based on a model computed for each gene or a group of genes in the MS training set group. The ascending order of genes reflects combinations of genes, where each row includes the gene specified in that row and in all preceding rows. For example, the average error presented in row number 4 reflects the average error in predicting a probability of a probable MS subject to develop the diagnosis of definite MS within a 2-years period using the group of genes described in rows 1, 2, 3 and 4 (i.e., SEQ ID NOs: 4, 16, 5 and 56). Probe set ID = Affymetrix ID.

As shown in Table 6 hereinabove, the predictive power of each set of genes was evaluated using the MS training and test sets of samples. The polynucleotide exhibiting the best predictive power in determining the probability of a probable MS subject to convert to the diagnosis of definite MS was the polynucleotide set forth by SEQ ID NO:4 (GenBank Accession No. AI860341; row No. 1 in Table 6), in which the average error between the test and training groups was 0.216. Similarly, the combination genes set forth by SEQ ID NOs:4 and 16 (GenBank Accession No. NM_(—)017975; row No. 2 in Table 6) displayed a predictive power with 0.216 average error. Another exemplary combination, which provides an even higher prediction power (with a smaller average error) is shown in row number 6 in Table 6, in which the combination of the polynucleotide sequences set forth in SEQ ID NOs:4, 16, 5, 56, 20 and 3 displayed a high predictive power with 0.158 average error. Yet another exemplary combination, which provides an even higher prediction power (with a smaller average error) is shown in row number 35 in Table 6, in which the combination of the polynucleotide sequences set forth in SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29 and 23 displayed a high predictive power with 0.132 average error. Thus, this analysis enables one skilled in the art to select a group of polynucleotides which can give the best predictive power for prediction of the probability of a subject diagnosed with probable MS (after the first neurological attack) to develop the diagnosis of definite MS within 2 years.

CONCLUSIONS

1. PBMC gene expression signature distinguished probable MS patients from healthy subjects.

2. Patients that experience a second relapse and converted to definite MS during 2 years of follow-up period have a specific gene expression signature.

3. Patients with probable and definite MS demonstrate a universal gene expression signature.

It is appreciated that certain features of the invention, which are, for clarity, described in the context of separate embodiments, may also be provided in combination in a single embodiment. Conversely, various features of the invention, which are, for brevity, described in the context of a single embodiment, may also be provided separately or in any suitable subcombination.

Although the invention has been described in conjunction with specific embodiments thereof, it is evident that many alternatives, modifications and variations will be apparent to those skilled in the art. Accordingly, it is intended to embrace all such alternatives, modifications and variations that fall within the spirit and broad scope of the appended claims. All publications, patents and patent applications mentioned in this specification are herein incorporated in their entirety by reference into the specification, to the same extent as if each individual publication, patent or patent application was specifically and individually indicated to be incorporated herein by reference. In addition, citation or identification of any reference in this application shall not be construed as an admission that such reference is available as prior art to the present invention.

REFERENCES Additional References are Cited in Text

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1. A method of determining a probability of a subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis, comprising determining in a cell of the subject a level of expression of at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and 39, wherein an alteration above a predetermined threshold in said level of expression of said at least one polynucleotide sequence in said cell of the subject relative to a level of expression of said at least one polynucleotide sequence in a reference cell is indicative of the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis.
 2. A method of treating a subject diagnosed with probable multiple sclerosis, comprising: (a) determining the probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis according to the method of claim 1, and; (b) selecting a treatment regimen based on said probability; thereby treating the subject diagnosed with probable multiple sclerosis. 3.-4. (canceled)
 5. A probeset comprising a plurality of oligonucleotides and no more than 500 oligonucleotides wherein each of said plurality of oligonucleotides is capable of specifically recognizing at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and
 39. 6. The probeset of claim 5, wherein each of said isolated nucleic acid sequences or said plurality of oligonucleotides is bound to a solid support.
 7. The probeset of claim 5, wherein said plurality oligonucleotides are bound to said solid support in an addressable location.
 8. The method of claim 1, wherein said reference cell is of an unaffected subject.
 9. The method of claim 8, wherein said alteration is upregulation of said expression level of said at least one polynucleotide sequence in said cell of the subject relative to said reference cell, whereas said at least one polynucleotide sequence is selected from the group consisting of SEQ ID NOs: 32-58.
 10. The method of claim 9, wherein said probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis is higher than about 75%.
 11. The method of claim 8, wherein said alteration is downregulation of said expression level of said at least one polynucleotide sequence in said cell of the subject relative to said reference cell, whereas said at least one polynucleotide sequence is selected from the group consisting of SEQ ID NOs: 1-31.
 12. The method of claim 11, wherein said probability of the subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis is higher than about 75%.
 13. The method of claim 1, wherein said detecting said level of expression is effected using an RNA detection method. 14.-15. (canceled)
 16. The method of claim 1, wherein said at least one polynucleotide sequence is as set forth by the polynucleotide sequences of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and
 39. 17. The method of claim 1, wherein said cell of the subject is a blood cell.
 18. The method of claim 1, wherein said detecting said level of expression is effected at the protein level.
 19. A kit for determining a probability of a subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis, comprising the probeset of claim 5 and a reference cell.
 20. The kit of claim 19, further comprising at least one reagent suitable for detecting hybridization of said plurality of oligonucleotides and at least one RNA transcript corresponding to said at least one polynucleotide sequence selected from the group consisting of SEQ ID NOs:4, 16, 5, 56, 20, 3, 1, 10, 57, 24, 14, 49, 13, 37, 6, 47, 50, 21, 46, 8, 26, 2, 15, 51, 44, 19, 17, 25, 33, 48, 36, 34, 12, 29, 23, 11, 45, 53, 41, 40, 31, 58, 27, 43, 35, 30, 52, 55, 7, 9, 42, 28, 54, 32, 22, 18, 38, and
 39. 21. The kit of claim 19, further comprising packaging materials packaging said at least one reagent and instructions for use in determining the probability of a subject diagnosed with probable multiple sclerosis to develop definite multiple sclerosis. 